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Catapano A, Cimmino F, Petrella L, Pizzella A, D'Angelo M, Ambrosio K, Marino F, Sabbatini A, Petrelli M, Paolini B, Lucchin L, Cavaliere G, Cristino L, Crispino M, Trinchese G, Mollica MP. Iron metabolism and ferroptosis in health and diseases: The crucial role of mitochondria in metabolically active tissues. J Nutr Biochem 2025; 140:109888. [PMID: 40057002 DOI: 10.1016/j.jnutbio.2025.109888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 11/15/2024] [Accepted: 02/27/2025] [Indexed: 03/30/2025]
Abstract
Iron is essential in various physiological processes, but its accumulation leads to oxidative stress and cell damage, thus iron homeostasis has to be tightly regulated. Ferroptosis is an iron-dependent non-apoptotic regulated cell death characterized by iron overload and reactive oxygen species accumulation. Mitochondria are organelles playing a crucial role in iron metabolism and involved in ferroptosis. MitoNEET, a protein of mitochondrial outer membrane, is a key element in this process. Ferroptosis, altering iron levels in several metabolically active organs, is linked to several non-communicable diseases. For example, iron overload in the liver leads to hepatic fibrosis and cirrhosis, accelerating non-alcholic fatty liver diseases progression, in the muscle cells contributes to oxidative damage leading to sarcopenia, and in the brain is associated to neurodegeneration. The aim of this review is to investigate the intricate balance of iron regulation focusing on the role of mitochondria and oxidative stress, and analyzing the ferroptosis implications in health and disease.
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Affiliation(s)
- Angela Catapano
- Department of Biology, University of Naples Federico II, Naples, Italy
| | - Fabiano Cimmino
- Department of Biology, University of Naples Federico II, Naples, Italy; Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Lidia Petrella
- Department of Biology, University of Naples Federico II, Naples, Italy
| | - Amelia Pizzella
- Department of Biology, University of Naples Federico II, Naples, Italy
| | - Margherita D'Angelo
- Department of Experimental Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Katia Ambrosio
- Department of Biology, University of Naples Federico II, Naples, Italy
| | - Francesca Marino
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Annarita Sabbatini
- Dietetic and Clinical Nutrition Unit, IEO European Institute of Oncology IRCSS, Milan, Italy
| | - Massimiliano Petrelli
- Department of Clinical and Molecular Sciences, Clinic of Endocrinology and Metabolic Diseases, Università Politecnica delle Marche, Ancona, Italy
| | - Barbara Paolini
- Department of Innovation, experimentation and clinical research, Unit of dietetics and clinical nutrition, S. Maria Alle Scotte Hospital, University of Siena, Siena, Italy
| | - Lucio Lucchin
- Dietetics and Clinical Nutrition, Bolzano Health District, Bolzano, Italy
| | - Gina Cavaliere
- Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy
| | - Luigia Cristino
- Institute of Biomolecular Chemistry, National Research Council of Italy, Pozzuoli, Naples, Italy
| | - Marianna Crispino
- Department of Biology, University of Naples Federico II, Naples, Italy.
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Marino F, Petrella L, Cimmino F, Pizzella A, Monda A, Allocca S, Rotondo R, D’Angelo M, Musco N, Iommelli P, Catapano A, Bagnato C, Paolini B, Cavaliere G. From Obesity to Mitochondrial Dysfunction in Peripheral Tissues and in the Central Nervous System. Biomolecules 2025; 15:638. [PMID: 40427531 PMCID: PMC12108580 DOI: 10.3390/biom15050638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2025] [Revised: 04/25/2025] [Accepted: 04/26/2025] [Indexed: 05/29/2025] Open
Abstract
Obesity is a condition of chronic low-grade inflammation affecting peripheral organs of the body, as well as the central nervous system. The adipose tissue dysfunction occurring under conditions of obesity is a key factor in the onset and progression of a variety of diseases, including neurodegenerative disorders. Mitochondria, key organelles in the production of cellular energy, play an important role in this tissue dysfunction. Numerous studies highlight the close link between obesity and adipocyte mitochondrial dysfunction, resulting in excessive ROS production and adipose tissue inflammation. This inflammation is transmitted systemically, leading to metabolic disorders that also impact the central nervous system, where pro-inflammatory cytokines impair mitochondrial and cellular functions in different areas of the brain, leading to neurodegenerative diseases. To date, several bioactive compounds are able to prevent and/or slow down neurogenerative processes by acting on mitochondrial functions. Among these, some molecules present in the Mediterranean diet, such as polyphenols, carotenoids, and omega-3 PUFAs, exert a protective action due to their antioxidant and anti-inflammatory ability. The aim of this review is to provide an overview of the involvement of adipose tissue dysfunction in the development of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and multiple sclerosis, emphasizing the central role played by mitochondria, the main actors in the cross-talk between adipose tissue and the central nervous system.
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Affiliation(s)
- Francesca Marino
- Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy;
| | - Lidia Petrella
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy; (L.P.); (A.P.); (A.C.)
| | - Fabiano Cimmino
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy; (L.P.); (A.P.); (A.C.)
| | - Amelia Pizzella
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy; (L.P.); (A.P.); (A.C.)
| | - Antonietta Monda
- Department of Human Sciences and Quality of Life Promotion, San Raffaele Telematic University, 00166 Rome, Italy;
| | - Salvatore Allocca
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy;
| | - Roberta Rotondo
- Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy;
| | - Margherita D’Angelo
- Department of Biology, Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA;
| | - Nadia Musco
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy; (N.M.); (P.I.)
| | - Piera Iommelli
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy; (N.M.); (P.I.)
| | - Angela Catapano
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy; (L.P.); (A.P.); (A.C.)
| | - Carmela Bagnato
- Clinical Nutrition Unit, Madonna Delle Grazie Hospital, 75100 Matera, Italy;
| | - Barbara Paolini
- Unit of Dietetics and Clinical Nutrition, Department of Innovation, Experimentation and Clinical Research, S. Maria Alle Scotte Hospital, University of Siena, 53100 Siena, Italy;
| | - Gina Cavaliere
- Department of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, Italy
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Dakal TC, Xiao F, Bhusal CK, Sabapathy PC, Segal R, Chen J, Bai X. Lipids dysregulation in diseases: core concepts, targets and treatment strategies. Lipids Health Dis 2025; 24:61. [PMID: 39984909 PMCID: PMC11843775 DOI: 10.1186/s12944-024-02425-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Accepted: 12/30/2024] [Indexed: 02/23/2025] Open
Abstract
Lipid metabolism is a well-regulated process essential for maintaining cellular functions and energy homeostasis. Dysregulation of lipid metabolism is associated with various conditions, including cardiovascular diseases, neurodegenerative disorders, and metabolic syndromes. This review explores the mechanisms underlying lipid metabolism, emphasizing the roles of key lipid species such as triglycerides, phospholipids, sphingolipids, and sterols in cellular physiology and pathophysiology. It also examines the genetic and environmental factors contributing to lipid dysregulation and the challenges of diagnosing and managing lipid-related disorders. Recent advancements in lipid-lowering therapies, including PCSK9 inhibitors, ezetimibe, bempedoic acid, and olpasiran, provide promising treatment options. However, these advancements are accompanied by challenges related to cost, accessibility, and patient adherence. The review highlights the need for personalized medicine approaches to address the interplay between genetics and environmental factors in lipid metabolism. As lipidomics and advanced diagnostic tools continue to progress, a deeper understanding of lipid-related disorders could pave the way for more effective therapeutic strategies.
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Affiliation(s)
- Tikam Chand Dakal
- Genome and Computational Biology Lab, Mohanlal Sukhadia, University, Udaipur, 313001, India
| | - Feng Xiao
- Department of Gastroenterology, The Second Affiliated Hospital of Shandong First Medical University, Taian, 271000, China
| | - Chandra Kanta Bhusal
- Aarupadai Veedu Medical College and Hospital, VMRF-DU, Pondicherry, 607402, India
- Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | | | - Rakesh Segal
- Aarupadai Veedu Medical College and Hospital, VMRF-DU, Pondicherry, 607402, India
- Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Juan Chen
- Department of Gastroenterology, The Second Affiliated Hospital of Shandong First Medical University, Taian, 271000, China.
| | - Xiaodong Bai
- Department of Plastic Surgery, Southern University of Science and Technology Hospital, Shenzhen, 518055, China.
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Dimitriadis K, Iliakis P, Vakka A, Pyrpyris N, Pitsillidi A, Tsioufis P, Fragkoulis C, Hering D, Weil J, Kollias A, Konstantinidis D, Tsioufis K. Effects of Sympathetic Denervation in Metabolism Regulation: A Novel Approach for the Treatment of MASLD? Cardiol Rev 2025:00045415-990000000-00395. [PMID: 39750025 DOI: 10.1097/crd.0000000000000850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Although metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease, has become the most common chronic liver disorder, its complex pathophysiology has not been fully elucidated up to date. A correlation between elevated sympathetic activation and MASLD has been highlighted in recent preclinical and clinical studies. Furthermore, increased sympathetic activity has been associated with the main mechanisms involved in MASLD, such as lipid accumulation in the liver, insulin resistance, and metabolic dysregulation, while it has been also correlated with the progression of MASLD, leading to liver fibrosis. Preclinical studies demonstrated that therapies which ameliorate the activation of the sympathetic nervous system, such as renal and liver sympathetic denervation, reduce hepatic insulin resistance, decrease hepatic glucose production, and reverse hepatic steatosis in high-fat-diet models. However, data from clinical trials regarding the effect of renal denervation on metabolic parameters are conflicting, since several trials reported a favorable effect, while other trials stated no significant difference, with the profound limitation of the lack of originally designed denervation trials in this setting. Thus, a thorough review of the role of the sympathetic nervous system in the pathophysiology of MASLD, as well as the results of recent sympathetic denervation studies and trials regarding metabolic regulation and MASLD treatment would be of great importance.
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Affiliation(s)
- Kyriakos Dimitriadis
- From the First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Panagiotis Iliakis
- From the First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Angeliki Vakka
- From the First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Nikolaos Pyrpyris
- From the First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Anna Pitsillidi
- Department of Obstetrics and Gynecology, Rheinlandklinikum Dormagen, Dormagen, Germany
| | - Panagiotis Tsioufis
- From the First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Christos Fragkoulis
- From the First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Dagmara Hering
- Department of Hypertension and Diabetology, Medical University of Gdańsk, Gdańsk, Poland
| | - Joachim Weil
- Medizinische Klinik II, Sana Kliniken Lübeck GmbH, Lübeck, Germany
| | - Anastasios Kollias
- Hypertension Center STRIDE-7, National and Kapodistrian University of Athens, School of Medicine, Third Department of Medicine, Sotiria Hospital, Athens, Greece
| | - Dimitris Konstantinidis
- From the First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Konstantinos Tsioufis
- From the First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
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Smorenburg JN, Hodun K, McTavish PV, Wang C, Pinheiro MA, Wells KRD, Brunt KR, Nakamura MT, Chabowski A, Mutch DM. EPA/DHA but Not ALA Reduces Visceral Adiposity and Adipocyte Size in High Fat Diet-Induced Obese Delta-6 Desaturase Knockout Mice. Mol Nutr Food Res 2025; 69:e202400721. [PMID: 39707641 PMCID: PMC11744037 DOI: 10.1002/mnfr.202400721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 11/14/2024] [Accepted: 12/02/2024] [Indexed: 12/23/2024]
Abstract
The objective of this omega-3 feeding study was to elucidate the independent effects of α-linolenic acid (ALA) versus eicosapentaenoic (EPA)/docosahexaenoic acid (DHA) on visceral adiposity and inflammatory signaling in diet-induced obese delta-6 desaturase (Fads2) knockout (KO) mice. Male wildtype (WT) and Fads2 KO mice were fed a high-fat diet (45% kcal from fat) containing either lard (no omega-3s), flaxseed (ALA), or menhaden (EPA/DHA) for 21 weeks. Epididymal white adipose tissue (eWAT) was analyzed for changes in tissue weight, adipocyte size, triacylglycerol (TAG) and fatty acid content, and inflammatory markers. Despite no differences in final body weight, menhaden-fed mice had lower eWAT weight, smaller adipocytes, and lower TAG content compared to lard-fed mice regardless of Fads2 genotype. The eWAT of flaxseed-fed WT mice resembled menhaden-fed mice, while the eWAT of flaxseed-fed KO mice resembled lard-fed mice. No differences were observed in the expression of genes regulating eWAT inflammatory signaling (Tnfα, Nfκb, Mapk14, Mcp1, Ccl5, Tlr4, Nlrp3, or Adipoq) or the abundance of select proteins (p38-MAPK or MCP-1). In conclusion, a high-fat diet containing EPA/DHA, but not ALA, attenuates adipocyte hypertrophy and lowers TAG content but has no effect on eWAT inflammation in a mouse model of long-term diet-induced obesity.
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Affiliation(s)
- James N. Smorenburg
- Department of Human Health and Nutritional SciencesUniversity of GuelphGuelphOntarioCanada
| | - Katarzyna Hodun
- Department of PhysiologyMedical University of BialystokBialystokPoland
| | - Patrick V. McTavish
- Department of Human Health and Nutritional SciencesUniversity of GuelphGuelphOntarioCanada
| | - Chenxuan Wang
- Department of Human Health and Nutritional SciencesUniversity of GuelphGuelphOntarioCanada
| | | | - Kyle R. D. Wells
- Department of PharmacologyDalhousie UniversitySaint JohnNew BrunswickCanada
| | - Keith R. Brunt
- Department of PharmacologyDalhousie UniversitySaint JohnNew BrunswickCanada
| | - Manubu T. Nakamura
- Department of Food Science and Human NutritionUniversity of Illinois at Urbana‐ChampaignUrbanaIllinoisUSA
| | - Adrian Chabowski
- Department of PhysiologyMedical University of BialystokBialystokPoland
| | - David M. Mutch
- Department of Human Health and Nutritional SciencesUniversity of GuelphGuelphOntarioCanada
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Perdaens O, van Pesch V. Should We Consider Neurodegeneration by Itself or in a Triangulation with Neuroinflammation and Demyelination? The Example of Multiple Sclerosis and Beyond. Int J Mol Sci 2024; 25:12637. [PMID: 39684351 PMCID: PMC11641818 DOI: 10.3390/ijms252312637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 11/20/2024] [Accepted: 11/20/2024] [Indexed: 12/18/2024] Open
Abstract
Neurodegeneration is preeminent in many neurological diseases, and still a major burden we fail to manage in patient's care. Its pathogenesis is complicated, intricate, and far from being completely understood. Taking multiple sclerosis as an example, we propose that neurodegeneration is neither a cause nor a consequence by itself. Mitochondrial dysfunction, leading to energy deficiency and ion imbalance, plays a key role in neurodegeneration, and is partly caused by the oxidative stress generated by microglia and astrocytes. Nodal and paranodal disruption, with or without myelin alteration, is further involved. Myelin loss exposes the axons directly to the inflammatory and oxidative environment. Moreover, oligodendrocytes provide a singular metabolic and trophic support to axons, but do not emerge unscathed from the pathological events, by primary myelin defects and cell apoptosis or secondary to neuroinflammation or axonal damage. Hereby, trophic failure might be an overlooked contributor to neurodegeneration. Thus, a complex interplay between neuroinflammation, demyelination, and neurodegeneration, wherein each is primarily and secondarily involved, might offer a more comprehensive understanding of the pathogenesis and help establishing novel therapeutic strategies for many neurological diseases and beyond.
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Affiliation(s)
- Océane Perdaens
- Neurochemistry Group, Institute of NeuroScience, Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium;
| | - Vincent van Pesch
- Neurochemistry Group, Institute of NeuroScience, Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium;
- Department of Neurology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium
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Zheng D, Cai J, Xu S, Jiang S, Li C, Wang B. The association of triglyceride-glucose index and combined obesity indicators with chest pain and risk of cardiovascular disease in American population with pre-diabetes or diabetes. Front Endocrinol (Lausanne) 2024; 15:1471535. [PMID: 39309107 PMCID: PMC11412814 DOI: 10.3389/fendo.2024.1471535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Accepted: 08/19/2024] [Indexed: 09/25/2024] Open
Abstract
Aim To investigate the correlation of the triglyceride-glucose (TyG) index and its combined obesity indicators with chest pain and cardiovascular disease (CVD) in the pre-diabetes and diabetes population. Methods This cross-sectional investigation encompassed 6488 participants with diabetes and pre-diabetes who participated in the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016. The association of the TyG and combined obesity index with chest pain and CVD was investigated using weighted logistic regression models and restricted cubic spline (RCS) analysis. The receiver operating characteristic (ROC) curve analysis was performed to compare different indicators. Results In multivariate logistic regression fully adjusted for confounding variables, our analyses revealed significant associations between TyG, TyG-BMI, TyG-WC, and TyG-WHtR and chest pain, with adjusted ORs (95% CI) of 1.21 (1.05, 1.39), 1.06 (1.01, 1.11), 1.08 (1.04, 1.14), and 1.27 (1.08, 1.48), respectively. For total-CVD, the adjusted ORs (95% CI) were 1.32 (1.08, 1.61), 1.10 (1.03, 1.17), 1.13 (1.06, 1.19), and 1.63 (1.35, 1.97), respectively, among which TyG, TyG-WC, and TyG-WHtR present curvilinear associations in RCS analysis (all P-nonlinear < 0.05). Furthermore, the ROC curve showed that TyG-WC had the most robust predictive efficacy for total-CVD, coronary heart disease (CHD), and myocardial infarction (MI), while TyG-WHtR had the best predictive ability for angina and heart failure. Conclusion There are significant associations of TyG and its related indicators with chest pain and total-CVD among the pathoglycemia population. TyG-WC and TyG-WHtR demonstrated superior predictive capability for the incidence of cardiovascular events.
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Affiliation(s)
- Dongze Zheng
- Department of Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- Human Phenome Institute, Shantou University Medical College, Shantou, Guangdong, China
| | - Jiamiao Cai
- Department of Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- Human Phenome Institute, Shantou University Medical College, Shantou, Guangdong, China
| | - Sifan Xu
- Department of Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- Human Phenome Institute, Shantou University Medical College, Shantou, Guangdong, China
| | - Shiyan Jiang
- Department of Nephrology, Jieyang People’s Hospital, Jieyang, Guangdong, China
| | - Chenlin Li
- Department of Cardiology, Jieyang People’s Hospital, Jieyang, Guangdong, China
| | - Bin Wang
- Department of Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
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Bosello F, Vanzo A, Zaffalon C, Polinelli L, Saggin F, Bonacci E, Pedrotti E, Marchini G, Bosello O. Obesity, body fat distribution and eye diseases. Eat Weight Disord 2024; 29:33. [PMID: 38710948 PMCID: PMC11074037 DOI: 10.1007/s40519-024-01662-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 04/22/2024] [Indexed: 05/08/2024] Open
Abstract
BACKGROUND The prevalence of obesity, a chronic disease, is increasing, and obesity is now considered a global epidemic. Eye diseases are also increasing worldwide and have serious repercussions on quality of life as well as increasingly high costs for the community. The relationships between obesity and ocular pathologies are not yet well clarified and are not pathologically homogeneous: they seem to be somehow linked to excess body fat, especially to the distribution of adipose tissue and its ectopic deposits. PURPOSE Our objective was to examine the associations between obesity and anthropometric indices, including body mass index (BMI), waist circumference (WC), and the waist/hip ratio (WHR), and the risk of most widespread eye diseases, with particular attention given to the most significant metabolic mechanisms. METHODS This article provides a narrative overview of the effect of obesity and anthropometric measurements of body fat on prevalent eye diseases. We used the MEDLINE/PubMed, CINAHL, EMBASE, and Cochrane Library databases from 1984 to 2024. In addition, we hand-searched references from the retrieved articles and explored a number of related websites. A total of 153 publications were considered. RESULTS There is significant evidence that obesity is associated with several eye diseases. Waist circumference (WC) and the waist/hip ratio (WHR) have been observed to have stronger positive associations with eye diseases than BMI. CONCLUSIONS Obesity must be considered a significant risk factor for eye diseases; hence, a multidisciplinary and multidimensional approach to treating obesity, which also affects ocular health, is important. In the prevention and treatment of eye diseases related to obesity, lifestyle factors, especially diet and physical activity, as well as weight changes, both weight loss and weight gain, should not be overlooked. LEVEL OF EVIDENCE Level V narrative review.
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Affiliation(s)
- Francesca Bosello
- Department of Surgery, Dentistry, Maternity and Infant, Ophthalmology Clinic, University of Verona, Verona, Italy.
| | - Angiola Vanzo
- Food Hygiene and Nutrition Unit, Azienda ULSS 8, Berica, Veneto, Italy
| | - Chiara Zaffalon
- Department of Surgery, Dentistry, Maternity and Infant, Ophthalmology Clinic, University of Verona, Verona, Italy
| | - Luca Polinelli
- Department of Surgery, Dentistry, Maternity and Infant, Ophthalmology Clinic, University of Verona, Verona, Italy
| | - Filippo Saggin
- Department of Surgery, Dentistry, Maternity and Infant, Ophthalmology Clinic, University of Verona, Verona, Italy
| | - Erika Bonacci
- Department of Engineering for Innovation Medicine, Ophthalmology Clinic, University of Verona, Verona, Italy
| | - Emilio Pedrotti
- Department of Surgery, Dentistry, Maternity and Infant, Ophthalmology Clinic, University of Verona, Verona, Italy
| | - Giorgio Marchini
- Department of Surgery, Dentistry, Maternity and Infant, Ophthalmology Clinic, University of Verona, Verona, Italy
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Hu S, Xiong X, Qiu S, Li J, Xu H, Zhou X, Wang S, Wei Q, Yang L. Comparing Efficacies of Different Exercises on Androgen Deprivation Therapy Adverse Effects in Prostate Cancer Patients: A Network Meta-Analysis. Urol Int 2024; 108:298-313. [PMID: 38432212 DOI: 10.1159/000538114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Accepted: 01/31/2024] [Indexed: 03/05/2024]
Abstract
INTRODUCTION Previous studies showed exercise have efficacies for androgen deprivation therapy (ADT) adverse effects. To compare the efficacies of different exercises on ADT adverse effects, we conducted the network meta-analysis (NMA). METHODS Literature retrieval was performed in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL). Nineteen studies (1,184 participants) were included. All analyses were performed in R 4.1.2 or RevMan 5.4.1. RESULTS NMA results showed that compared with the control group, both aerobic + resistance training (ART) (MD = 5.92, 95% CI: 0.38; 11.46) and resistance exercise (RE) (MD = 5.62, 95% CI: 2.70; 8.55) improved quality of life (QoL). ART (P score: 0.72) may have superiority over RE (P score: 0.7). ART (MD = -10.89, 95% CI: -17.67; -4.11) significantly improved the performance of 400-m test. RE could significantly improve leg strength (MD = 118, 95% CI: 78.75; 157.25) and chest strength (MD = 13.30, 95% CI: 4.07; 22.53). RE ranked first for strength improvements of leg and chest. CONCLUSION ART showed better efficacy for the QoL and significantly improved the performance of 400-m test. RE might be superior for the strengths of leg and chest. ART may be appropriate for patients with less significant muscle strength decline but also other adverse effects of ADT, such as decreased cardiopulmonary function.
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Affiliation(s)
- Siping Hu
- Department of Urology, Institute of Urology and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China,
- West China School of Clinical Medicine, West China Hospital, Sichuan University, Chengdu, China,
| | - Xingyu Xiong
- Department of Urology, Institute of Urology and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China
- West China School of Clinical Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Shi Qiu
- Department of Urology, Institute of Urology and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China
- Center of Biomedical Big Data, West China Hospital, Sichuan University, Chengdu, China
| | - Jiakun Li
- Department of Urology, Institute of Urology and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China
- Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Hang Xu
- Department of Urology, Institute of Urology and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China
- West China School of Clinical Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Xianghong Zhou
- Department of Urology, Institute of Urology and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China
- West China School of Clinical Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Sheng Wang
- Department of Urology, Institute of Urology and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China
- West China School of Clinical Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Qiang Wei
- Department of Urology, Institute of Urology and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China
| | - Lu Yang
- Department of Urology, Institute of Urology and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China
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10
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Lin Z, Long F, Kang R, Klionsky DJ, Yang M, Tang D. The lipid basis of cell death and autophagy. Autophagy 2024; 20:469-488. [PMID: 37768124 PMCID: PMC10936693 DOI: 10.1080/15548627.2023.2259732] [Citation(s) in RCA: 22] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 08/25/2023] [Accepted: 09/12/2023] [Indexed: 09/29/2023] Open
Abstract
ABBREVIATIONS ACSL: acyl-CoA synthetase long chain family; DISC: death-inducing signaling complex; DAMPs: danger/damage-associated molecular patterns; Dtgn: dispersed trans-Golgi network; FAR1: fatty acyl-CoA reductase 1; GPX4: glutathione peroxidase 4; LPCAT3: lysophosphatidylcholine acyltransferase 3; LPS: lipopolysaccharide; MUFAs: monounsaturated fatty acids; MOMP: mitochondrial outer membrane permeabilization; MLKL, mixed lineage kinase domain like pseudokinase; oxPAPC: oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine; OxPCs: oxidized phosphatidylcholines; PUFAs: polyunsaturated fatty acids; POR: cytochrome p450 oxidoreductase; PUFAs: polyunsaturated fatty acids; RCD: regulated cell death; RIPK1: receptor interacting serine/threonine kinase 1; SPHK1: sphingosine kinase 1; SOAT1: sterol O-acyltransferase 1; SCP2: sterol carrier protein 2; SFAs: saturated fatty acids; SLC47A1: solute carrier family 47 member 1; SCD: stearoyl-CoA desaturase; VLCFA: very long chain fatty acids.
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Affiliation(s)
- Zhi Lin
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Hunan Clinical Research Center of Pediatric Cancer, Changsha, Hunan, China
| | - Fei Long
- Department of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Postdoctoral Research Station of Basic Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Rui Kang
- Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA
| | - Daniel J. Klionsky
- Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA
| | - Minghua Yang
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Hunan Clinical Research Center of Pediatric Cancer, Changsha, Hunan, China
| | - Daolin Tang
- Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA
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11
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Trinchese G, Cimmino F, Catapano A, Cavaliere G, Mollica MP. Mitochondria: the gatekeepers between metabolism and immunity. Front Immunol 2024; 15:1334006. [PMID: 38464536 PMCID: PMC10920337 DOI: 10.3389/fimmu.2024.1334006] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 02/08/2024] [Indexed: 03/12/2024] Open
Abstract
Metabolism and immunity are crucial monitors of the whole-body homeodynamics. All cells require energy to perform their basic functions. One of the most important metabolic skills of the cell is the ability to optimally adapt metabolism according to demand or availability, known as metabolic flexibility. The immune cells, first line of host defense that circulate in the body and migrate between tissues, need to function also in environments in which nutrients are not always available. The resilience of immune cells consists precisely in their high adaptive capacity, a challenge that arises especially in the framework of sustained immune responses. Pubmed and Scopus databases were consulted to construct the extensive background explored in this review, from the Kennedy and Lehninger studies on mitochondrial biochemistry of the 1950s to the most recent findings on immunometabolism. In detail, we first focus on how metabolic reconfiguration influences the action steps of the immune system and modulates immune cell fate and function. Then, we highlighted the evidence for considering mitochondria, besides conventional cellular energy suppliers, as the powerhouses of immunometabolism. Finally, we explored the main immunometabolic hubs in the organism emphasizing in them the reciprocal impact between metabolic and immune components in both physiological and pathological conditions.
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Affiliation(s)
| | - Fabiano Cimmino
- Department of Biology, University of Naples Federico II, Naples, Italy
| | - Angela Catapano
- Department of Biology, University of Naples Federico II, Naples, Italy
| | - Gina Cavaliere
- Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy
| | - Maria Pina Mollica
- Department of Biology, University of Naples Federico II, Naples, Italy
- Task Force on Microbiome Studies, University of Naples Federico II, Naples, Italy
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12
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Liu L, Peng J, Wang N, Wu Z, Zhang Y, Cui H, Zang D, Lu F, Ma X, Yang J. Comparison of seven surrogate insulin resistance indexes for prediction of incident coronary heart disease risk: a 10-year prospective cohort study. Front Endocrinol (Lausanne) 2024; 15:1290226. [PMID: 38323107 PMCID: PMC10844492 DOI: 10.3389/fendo.2024.1290226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 01/08/2024] [Indexed: 02/08/2024] Open
Abstract
Background There were seven novel and easily accessed insulin resistance (IR) surrogates established, including the Chinese visceral adiposity index (CVAI), the visceral adiposity index (VAI), lipid accumulation product (LAP), triglyceride glucose (TyG) index, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC) and TyG-waist to height ratio (TyG-WHtR). We aimed to explore the association between the seven IR surrogates and incident coronary heart disease (CHD), and to compare their predictive powers among Chinese population. Methods This is a 10-year prospective cohort study conducted in China including 6393 participants without cardiovascular disease (CVD) at baseline. We developed Cox regression analyses to examine the association of IR surrogates with CHD (hazard ratio [HR], 95% confidence intervals [CI]). Moreover, the receiver operating characteristic (ROC) curve was performed to compare the predictive values of these indexes for incident CHD by the areas under the ROC curve (AUC). Results During a median follow-up period of 10.25 years, 246 individuals newly developed CHD. Significant associations of the IR surrogates (excepted for VAI) with incident CHD were found in our study after fully adjustment, and the fifth quintile HRs (95% CIs) for incident CHD were respectively 2.055(1.216-3.473), 1.446(0.948-2.205), 1.753(1.099-2.795), 2.013(1.214-3.339), 3.169(1.926-5.214), 2.275(1.391-3.719) and 2.309(1.419-3.759) for CVAI, VAI, LAP, TyG, TyG-BMI, TyG-WC and TyG-WHtR, compared with quintile 1. Furthermore, CVAI showed maximum predictive capacity for CHD among these seven IR surrogates with the largest AUC: 0.632(0.597,0.667). Conclusion The seven IR surrogates (excepted for VAI) were independently associated with higher prevalence of CHD, among which CVAI is the most powerful predictor for CHD incidence in Chinese populations.
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Affiliation(s)
- Li Liu
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Jie Peng
- Department of Geriatric Medicine, Qilu Hospital of Shandong University, Key Laboratory of Cardiovascular Proteomics of Shandong Province, Jinan, China
| | - Ning Wang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Zhenguo Wu
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Yerui Zhang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Huiliang Cui
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Dejin Zang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Fanghong Lu
- Cardio-Cerebrovascular Control and Research Center, Shandong Academy of Medical Sciences, Jinan, China
| | - Xiaoping Ma
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
- Department of Obstetrics and Gynecology, LiaoCheng People’s Hospital, Liaocheng, China
| | - Jianmin Yang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
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13
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Zhang Y, Tang W, Tang B, Fan K, Zhao K, Fang X, Lin H. Altered mitochondrial lymphocyte in overweight schizophrenia patients treated with atypical antipsychotics and its association with cognitive function. Front Immunol 2024; 14:1325495. [PMID: 38235140 PMCID: PMC10791827 DOI: 10.3389/fimmu.2023.1325495] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Accepted: 12/08/2023] [Indexed: 01/19/2024] Open
Abstract
Objective Increasing evidence indicated that schizophrenia and obesity are associated with altered mitochondrial and immune function. In this study, we investigated the levels of CRP (C-reactive protein) and mitochondrial lymphocytes in chronically treated schizophrenia patients with atypical antipsychotic medications and further explored the relationship between mitochondrial lymphocyte and weight gain as well as cognitive function in these patients. Methods We evaluated the mitochondrial lymphocyte count of 97 patients (53 overweight, 44 non-overweight) and 100 healthy controls using mitochondrial fluorescence staining and flow cytometry (NovoCyte, Agilent Technologies, US). The serum CRP was measured by high-sensitivity enzyme-linked immunosorbent assay (ELISA). Clinical symptoms and cognitive function of the patients were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Results The results showed that mitochondrial lymphocyte counts of CD3+ T, CD3+CD4+ T, and CD3+CD8+ T cells in schizophrenia patients were higher than in the control group (p < 0.05). Additionally, overweight patients had significantly higher mitochondrial lymphocyte counts of CD3+ T and CD3+CD4+ T cells compared to schizophrenia patients with normal weight. Stratified analysis by gender revealed that there was a statistically significant difference in CD3+CD4+ mitochondrial lymphocyte count in male patients (p = 0.014) and a marginal trend toward significance in female patients (p = 0.058). Furthermore, the mitochondrial lymphocyte counts of CD3+ T and CD3+CD4+ T cells, as well as CRP levels, were positively correlated with BMI in schizophrenia patients, but the mitochondrial lymphocyte counts of CD3+CD4+ T cells were negatively correlated with the language scale in the RBANS. Conclusion Our study results provide evidence for the association between altered mitochondrial T lymphocyte and weight gain as well as cognitive impairment in schizophrenia patients treated with atypical antipsychotic medications.
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Affiliation(s)
- Yaoyao Zhang
- Department of Psychiatry, The Affiliated Kangning Hospital of Wenzhou Medical University Zhejiang Provincial Clinical Research Center for Mental Disorder, Wenzhou, Zhejiang, China
| | - Wei Tang
- Department of Psychiatry, The Affiliated Kangning Hospital of Wenzhou Medical University Zhejiang Provincial Clinical Research Center for Mental Disorder, Wenzhou, Zhejiang, China
| | - Bei Tang
- Department of Education, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Kaili Fan
- Department of Psychiatry, Wenzhou Seventh People’s Hospital, Wenzhou, Zhejiang, China
| | - Ke Zhao
- Department of Psychiatry, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xinyu Fang
- Department of Psychiatry, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Hui Lin
- Department of Psychiatry, The Second People`s Hospital of YuHuan, Taizhou, Zhejiang, China
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14
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Engin A. The Unrestrained Overeating Behavior and Clinical Perspective. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1460:167-198. [PMID: 39287852 DOI: 10.1007/978-3-031-63657-8_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/19/2024]
Abstract
Obesity-related co-morbidities decrease life quality, reduce working ability, and lead to early death. In the adult population, eating addiction manifests with excessive food consumption and the unrestrained overeating behavior, which is associated with increased risk of morbidity and mortality and defined as the binge eating disorder (BED). This hedonic intake is correlated with fat preference and the total amount of dietary fat consumption is the most potent risk factor for weight gain. Long-term BED leads to greater sensitivity to the rewarding effects of palatable foods and results in obesity fatefully. Increased plasma concentrations of non-esterified free fatty acids and lipid-overloaded hypertrophic adipocytes may cause insulin resistance. In addition to dietary intake of high-fat diet, sedentary lifestyle leads to increased storage of triglycerides not only in adipose tissue but also ectopically in other tissues. Lipid-induced apoptosis, ceramide accumulation, reactive oxygen species overproduction, endoplasmic reticulum stress, and mitochondrial dysfunction play role in the pathogenesis of lipotoxicity. Food addiction and BED originate from complex action of dopaminergic, opioid, and cannabinoid systems. BED may also be associated with both obesity and major depressive disorder. For preventing morbidity and mortality, as well as decreasing the impact of obesity-related comorbidities in appropriately selected patients, opiate receptor antagonists and antidepressant combination are recommended. Pharmacotherapy alongside behavioral management improves quality of life and reduces the obesity risk; however, the number of licensed drugs is very few. Thus, stereotactic treatment is recommended to break down the refractory obesity and binge eating in obese patient. As recent applications in the field of non-invasive neuromodulation, transcranial magnetic stimulation and transcranial direct current stimulation are thought to be important in image-guided deep brain stimulation in humans. Chronic overnutrition most likely provides repetitive and persistent signals that up-regulate inhibitor of nuclear factor kappa B (NF-κB) kinase beta subunit/NF-κB (IKKβ/NF-κB) in the hypothalamus before the onset of obesity. However, how the mechanisms of high-fat diet-induced peripheral signals affect the hypothalamic arcuate nucleus remain largely unknown.
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Affiliation(s)
- Atilla Engin
- Faculty of Medicine, Department of General Surgery, Gazi University, Besevler, Ankara, Turkey.
- Mustafa Kemal Mah. 2137. Sok. 8/14, 06520, Cankaya, Ankara, Turkey.
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15
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Yoon J, Heo SJ, Lee JH, Kwon YJ, Lee JE. Comparison of METS-IR and HOMA-IR for predicting new-onset CKD in middle-aged and older adults. Diabetol Metab Syndr 2023; 15:230. [PMID: 37957738 PMCID: PMC10644442 DOI: 10.1186/s13098-023-01214-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Accepted: 11/05/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND Chronic kidney disease (CKD) has emerged as a mounting public health issue worldwide; therefore, prompt identification and prevention are imperative in mitigating CKD-associated complications and mortality rate. We aimed to compare the predictive powers of the homeostatic model assessment for insulin resistance (HOMA-IR) and the metabolic score for insulin resistance (METS-IR) for CKD incidence in middle-aged and older adults. METHODS This study used longitudinal prospective cohort data from the Korean Genome and Epidemiology Study. A total of 10,030 participants, aged 40-69 years, residing in the Ansung or Ansan regions of the Republic of Korea, were recruited between 2001 and 2002 through a two-stage cluster sampling method. We compared the predictive powers of METS-IR and HOMA-IR for CKD prevalence and incidence, respectively. CKD prevalence was measured by the area under the receiver operating characteristic (ROC) curve (AUC), and the indices' predictive performance for CKD incidence were assessed using Harrell's concordance index and time-dependent ROC curve analysis. RESULTS A total of 9261 adults aged 40-69 years at baseline and 8243 adults without CKD were included in this study. The AUCs and 95% confidence intervals (CIs) of HOMA-IR and METS-IR for CKD prevalence at baseline were 0.577 (0.537-0.618) and 0.599 (0.560-0.637), respectively, with no significant difference (p = 0.337). The Heagerty's integrated AUC for METS-IR in predicting CKD incidence was 0.772 (95% CI 0.750-0.799), which was significantly higher than that of HOMA-IR (0.767 [95% CI 0.742-0.791], p = 0.015). CONCLUSION METS-IR surpassed HOMA-IR in predicting CKD incidence and was as effective as HOMA-IR in predicting CKD prevalence. This implies that METS-IR could be a valuable indicator for early detection and prevention of CKD among Korean adults.
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Affiliation(s)
- Jihyun Yoon
- Department of Family Medicine, Anam Hospital, Korea University College of Medicine, 73 Goryeodae-ro, Seongbuk-gu, Seoul, 02481, Republic of Korea
| | - Seok-Jae Heo
- Division of Biostatistics, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea
| | - Jun-Hyuk Lee
- Department of Family Medicine, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul, 01830, Republic of Korea
- Department of Medicine, Hanyang University Graduate School of Medicine, Seoul, 04763, Republic of Korea
| | - Yu-Jin Kwon
- Department of Family Medicine, Yonsei University of College of Medicine, Yongin Severance Hospital, Yongin, 16995, Republic of Korea.
| | - Jung Eun Lee
- Division of Nephrology, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Gyeonggi, Republic of Korea.
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16
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Neto A, Fernandes A, Barateiro A. The complex relationship between obesity and neurodegenerative diseases: an updated review. Front Cell Neurosci 2023; 17:1294420. [PMID: 38026693 PMCID: PMC10665538 DOI: 10.3389/fncel.2023.1294420] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 10/23/2023] [Indexed: 12/01/2023] Open
Abstract
Obesity is a global epidemic, affecting roughly 30% of the world's population and predicted to rise. This disease results from genetic, behavioral, societal, and environmental factors, leading to excessive fat accumulation, due to insufficient energy expenditure. The adipose tissue, once seen as a simple storage depot, is now recognized as a complex organ with various functions, including hormone regulation and modulation of metabolism, inflammation, and homeostasis. Obesity is associated with a low-grade inflammatory state and has been linked to neurodegenerative diseases like multiple sclerosis (MS), Alzheimer's (AD), and Parkinson's (PD). Mechanistically, reduced adipose expandability leads to hypertrophic adipocytes, triggering inflammation, insulin and leptin resistance, blood-brain barrier disruption, altered brain metabolism, neuronal inflammation, brain atrophy, and cognitive decline. Obesity impacts neurodegenerative disorders through shared underlying mechanisms, underscoring its potential as a modifiable risk factor for these diseases. Nevertheless, further research is needed to fully grasp the intricate connections between obesity and neurodegeneration. Collaborative efforts in this field hold promise for innovative strategies to address this complex relationship and develop effective prevention and treatment methods, which also includes specific diets and physical activities, ultimately improving quality of life and health.
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Affiliation(s)
- Alexandre Neto
- Central Nervous System, Blood and Peripheral Inflammation, Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal
| | - Adelaide Fernandes
- Central Nervous System, Blood and Peripheral Inflammation, Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal
- Department of Pharmaceutical Sciences and Medicines, Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal
| | - Andreia Barateiro
- Central Nervous System, Blood and Peripheral Inflammation, Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal
- Department of Pharmaceutical Sciences and Medicines, Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal
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17
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Saha A, Kolonin MG, DiGiovanni J. Obesity and prostate cancer - microenvironmental roles of adipose tissue. Nat Rev Urol 2023; 20:579-596. [PMID: 37198266 DOI: 10.1038/s41585-023-00764-9] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/24/2023] [Indexed: 05/19/2023]
Abstract
Obesity is known to have important roles in driving prostate cancer aggressiveness and increased mortality. Multiple mechanisms have been postulated for these clinical observations, including effects of diet and lifestyle, systemic changes in energy balance and hormonal regulation and activation of signalling by growth factors and cytokines and other components of the immune system. Over the past decade, research on obesity has shifted towards investigating the role of peri-prostatic white adipose tissue as an important source of locally produced factors that stimulate prostate cancer progression. Cells that comprise white adipose tissue, the adipocytes and their progenitor adipose stromal cells (ASCs), which proliferate to accommodate white adipose tissue expansion in obesity, have been identified as important drivers of obesity-associated cancer progression. Accumulating evidence suggests that adipocytes are a source of lipids that are used by adjacent prostate cancer cells. However, results of preclinical studies indicate that ASCs promote tumour growth by remodelling extracellular matrix and supporting neovascularization, contributing to the recruitment of immunosuppressive cells, and inducing epithelial-mesenchymal transition through paracrine signalling. Because epithelial-mesenchymal transition is associated with cancer chemotherapy resistance and metastasis, ASCs are considered to be potential targets of therapies that could be developed to suppress cancer aggressiveness in patients with obesity.
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Affiliation(s)
- Achinto Saha
- Division of Pharmacology and Toxicology and Dell Paediatric Research Institute, The University of Texas at Austin, Austin, TX, USA
- Center for Molecular Carcinogenesis and Toxicology, The University of Texas at Austin, Austin, TX, USA
- Livestrong Cancer Institutes, Dell Medical School, The University of Texas at Austin, Austin, TX, USA
| | - Mikhail G Kolonin
- The Brown Foundation Institute of Molecular Medicine for the Prevention of Disease, The University of Texas Health Sciences Center at Houston, Houston, Texas, USA.
| | - John DiGiovanni
- Division of Pharmacology and Toxicology and Dell Paediatric Research Institute, The University of Texas at Austin, Austin, TX, USA.
- Center for Molecular Carcinogenesis and Toxicology, The University of Texas at Austin, Austin, TX, USA.
- Livestrong Cancer Institutes, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
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Panico G, Fasciolo G, Migliaccio V, De Matteis R, Lionetti L, Napolitano G, Agnisola C, Venditti P, Lombardi A. 1,3-Butanediol Administration Increases β-Hydroxybutyrate Plasma Levels and Affects Redox Homeostasis, Endoplasmic Reticulum Stress, and Adipokine Production in Rat Gonadal Adipose Tissue. Antioxidants (Basel) 2023; 12:1471. [PMID: 37508009 PMCID: PMC10376816 DOI: 10.3390/antiox12071471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 07/15/2023] [Accepted: 07/19/2023] [Indexed: 07/30/2023] Open
Abstract
Ketone bodies (KBs) are an alternative energy source under starvation and play multiple roles as signaling molecules regulating energy and metabolic homeostasis. The mechanism by which KBs influence visceral white adipose tissue physiology is only partially known, and our study aimed to shed light on the effects they exert on such tissue. To this aim, we administered 1,3-butanediol (BD) to rats since it rapidly enhances β-hydroxybutyrate serum levels, and we evaluated the effect it induces within 3 h or after 14 days of treatment. After 14 days of treatment, rats showed a decrease in body weight gain, energy intake, gonadal-WAT (gWAT) weight, and adipocyte size compared to the control. BD exerted a pronounced antioxidant effect and directed redox homeostasis toward reductive stress, already evident within 3 h after its administration. BD lowered tissue ROS levels and oxidative damage to lipids and proteins and enhanced tissue soluble and enzymatic antioxidant capacity as well as nuclear erythroid factor-2 protein levels. BD also reduced specific mitochondrial maximal oxidative capacity and induced endoplasmic reticulum stress as well as interrelated processes, leading to changes in the level of adipokines/cytokines involved in inflammation, macrophage infiltration into gWAT, adipocyte differentiation, and lipolysis.
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Affiliation(s)
- Giuliana Panico
- Department of Biology, University of Naples Federico II, Complesso Monte Sant'Angelo Via Cintia 26, 80126 Napoli, Italy
| | - Gianluca Fasciolo
- Department of Biology, University of Naples Federico II, Complesso Monte Sant'Angelo Via Cintia 26, 80126 Napoli, Italy
| | - Vincenzo Migliaccio
- Department of Chemistry and Biology "A. Zambelli", University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, Italy
| | - Rita De Matteis
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
| | - Lillà Lionetti
- Department of Chemistry and Biology "A. Zambelli", University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, Italy
| | - Gaetana Napolitano
- Department of Science and Technology, Parthenope University of Naples, 80143 Naples, Italy
| | - Claudio Agnisola
- Department of Biology, University of Naples Federico II, Complesso Monte Sant'Angelo Via Cintia 26, 80126 Napoli, Italy
| | - Paola Venditti
- Department of Biology, University of Naples Federico II, Complesso Monte Sant'Angelo Via Cintia 26, 80126 Napoli, Italy
| | - Assunta Lombardi
- Department of Biology, University of Naples Federico II, Complesso Monte Sant'Angelo Via Cintia 26, 80126 Napoli, Italy
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19
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Cavaliere G, Cimmino F, Trinchese G, Catapano A, Petrella L, D'Angelo M, Lucchin L, Mollica MP. From Obesity-Induced Low-Grade Inflammation to Lipotoxicity and Mitochondrial Dysfunction: Altered Multi-Crosstalk between Adipose Tissue and Metabolically Active Organs. Antioxidants (Basel) 2023; 12:1172. [PMID: 37371902 DOI: 10.3390/antiox12061172] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 05/23/2023] [Accepted: 05/27/2023] [Indexed: 06/29/2023] Open
Abstract
Obesity is a major risk factor for several metabolic diseases, including type 2 diabetes, hyperlipidemia, cardiovascular diseases, and brain disorders. Growing evidence suggests the importance of inter-organ metabolic communication for the progression of obesity and the subsequent onset of related disorders. This review provides a broad overview of the pathophysiological processes that from adipose tissue dysfunction leading to altered multi-tissue crosstalk relevant to regulating energy homeostasis and the etiology of obesity. First, a comprehensive description of the role of adipose tissue was reported. Then, attention was turned toward the unhealthy expansion of adipose tissue, low-grade inflammatory state, metabolic inflexibility, and mitochondrial dysfunction as root causes of systemic metabolic alterations. In addition, a short spot was devoted to iron deficiency in obese conditions and the role of the hepcidin-ferroportin relationship in the management of this issue. Finally, different classes of bioactive food components were described with a perspective to enhance their potential preventive and therapeutic use against obesity-related diseases.
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Affiliation(s)
- Gina Cavaliere
- Department of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, Italy
- Centro Servizi Metrologici e Tecnologici Avanzati (CeSMA), Complesso Universitario di Monte Sant'Angelo, 80126 Naples, Italy
| | - Fabiano Cimmino
- Centro Servizi Metrologici e Tecnologici Avanzati (CeSMA), Complesso Universitario di Monte Sant'Angelo, 80126 Naples, Italy
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy
| | - Giovanna Trinchese
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy
| | - Angela Catapano
- Centro Servizi Metrologici e Tecnologici Avanzati (CeSMA), Complesso Universitario di Monte Sant'Angelo, 80126 Naples, Italy
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy
| | - Lidia Petrella
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy
| | - Margherita D'Angelo
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy
| | - Lucio Lucchin
- Dietetics and Clinical Nutrition, Bolzano Health District, 39100 Bolzano, Italy
| | - Maria Pina Mollica
- Centro Servizi Metrologici e Tecnologici Avanzati (CeSMA), Complesso Universitario di Monte Sant'Angelo, 80126 Naples, Italy
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy
- Task Force on Microbiome Studies, University of Naples Federico II, 80138 Naples, Italy
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20
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Denton JJ, Cedillo YE. Investigating family history of diabetes as a predictor of fasting insulin and fasting glucose activity in a sample of healthy weight adults. Acta Diabetol 2023; 60:535-543. [PMID: 36637530 DOI: 10.1007/s00592-023-02030-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 01/04/2023] [Indexed: 01/14/2023]
Abstract
AIMS Type 2 diabetes is a major public health problem for the global community. Having a family history of diabetes significantly increases risk for diabetes development and understanding how family history contributes to diabetes risk could lead to more effective prevention efforts for at-risk individuals. In a previous study, we showed family history of diabetes is a significant predictor of fasting insulin in healthy weight children. The present study aimed to use the National Health and Nutrition Examination Survey (NHANES 2017) to apply similar multiple regression models to a population of healthy weight adults to determine if family history is a significant predictor of fasting glucose and fasting insulin. METHODS Fasting glucose (mg/dL) and fasting insulin (pmol/L) were used as dependent variables in each model, respectively, with family history of diabetes as the independent variable. Covariates for each model included age, gender, race/ethnicity, waist circumference, and macronutrient intake. RESULTS The model significantly predicted the variance of fasting glucose [(F(11,364) = 34.80, p < 0.001, R2 = 0.2342] and fasting insulin [F(11,343) = 17.58, p < 0.001, R2 = 0.1162]. After adjusting for covariates, family history was a significant predicator of fasting glucose (p = 0.0193) as well as age, gender, non-Hispanic black ethnicity, waist circumference, and fat intake. Significant predictors of fasting insulin included gender and waist circumference, but not family history (p = 0.8264). In addition, fasting glucose was higher in individuals with a family history of diabetes (p = 0.033). CONCLUSIONS These results add to the understanding of how family history influences the biomarkers that contribute to diabetes development. Knowledge of how family history of diabetes relates to fasting insulin and fasting glucose activity in healthy weight individuals can be used to design personalized screening and early prevention strategies.
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Affiliation(s)
- Jessica J Denton
- University of Alabama at Birmingham, School of Health Professions Building, Room 448, 1720 2nd Ave S., Birmingham, Alabama, 35294, USA.
| | - Yenni E Cedillo
- University of Alabama at Birmingham, Webb Building, Room 544, 1720 2nd Ave S., Birmingham, Alabama, 35294, USA
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21
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Crosstalk between Adipose Tissue and Hepatic Mitochondria in the Development of the Inflammation and Liver Injury during Ageing in High-Fat Diet Fed Rats. Int J Mol Sci 2023; 24:ijms24032967. [PMID: 36769289 PMCID: PMC9917792 DOI: 10.3390/ijms24032967] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 01/31/2023] [Accepted: 02/01/2023] [Indexed: 02/05/2023] Open
Abstract
Obesity is considered an epidemic disorder, due to an imbalance between energy consumption and metabolizable energy intake. This balance is increasingly disrupted during normal aging processes due to the progressive impairment of mechanisms that normally control energy homeostasis. Obesity is triggered by an excessive lipid depots but reflects systemic inflammation along with large adipocytes secreting proinflammatory adipokines, an increase of the free fatty acids levels in the bloodstream, and ectopic lipid accumulation. Hepatic fat accumulation is the most common cause of chronic liver disease, characterized by mitochondrial dysfunction with a consequent impaired fat metabolism and increased oxidative stress. Therefore, mitochondrial dysfunction is associated to hepatic lipid accumulation and related complications. In this study, we assessed the crosstalk between adipose tissue and liver, analyzing the time-course of changes in hepatic mitochondrial fatty acid oxidation capacity versus fatty acid storage, focusing on the contribution of adipose tissue inflammation to hepatic lipid accumulation, using a rodent model of high fat diet-induced obesity. Our results demonstrate that both high-fat diet-induced obesity and aging induce dysregulation of adipose tissue function and similar metabolic alterations mediated by mitochondrial function impairment and altered inflammatory profile. The high fat diet-induced obesity anticipates and exacerbates liver mitochondrial dysfunction that occurs with aging processes.
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22
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Lin Z, Yang M. Lipidomics Analysis in Ferroptosis. Methods Mol Biol 2023; 2712:149-156. [PMID: 37578703 DOI: 10.1007/978-1-0716-3433-2_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/15/2023]
Abstract
Ferroptosis is a form of regulated cell death that occurs due to abnormal lipid metabolism. Lipids, which have been identified in over 45,000 different molecular species, play essential roles in modulating basic life processes. The process of ferroptosis is highly reliant on various lipid species, with polyunsaturated fatty acids (PUFAs) playing a central role in driving this process. Recent advances in mass spectrometry-based lipidomics have led to a surge in studies on ferroptosis. To explore the mechanism of lipid homeostasis in ferroptosis, the development of lipidomics techniques is critical. Currently, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) are the most widely used analytical techniques in lipidomics. These techniques offer deeper insights into the complex lipid mechanisms that underlie ferroptosis.
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Affiliation(s)
- Zhi Lin
- Department of Pediatrics, The Third Xiangya Hospital Central South University, Changsha, Hunan, China
| | - Minghua Yang
- Department of Pediatrics, The Third Xiangya Hospital Central South University, Changsha, Hunan, China.
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23
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Di Majo D, Sardo P, Giglia G, Di Liberto V, Zummo FP, Zizzo MG, Caldara GF, Rappa F, Intili G, van Dijk RM, Gallo D, Ferraro G, Gambino G. Correlation of Metabolic Syndrome with Redox Homeostasis Biomarkers: Evidence from High-Fat Diet Model in Wistar Rats. Antioxidants (Basel) 2022; 12:antiox12010089. [PMID: 36670955 PMCID: PMC9854509 DOI: 10.3390/antiox12010089] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/24/2022] [Accepted: 12/27/2022] [Indexed: 01/03/2023] Open
Abstract
Metabolic Syndrome (MetS) is an extremely complex disease. A non-balanced diet such as high-fat diet (HFD) induces metabolic dysfunction that could modify redox homeostasis. We here aimed at exploring redox homeostasis in male Wistar rats, following 8 weeks of HFD, correlating the eventual modification of selected biomarkers that could be associated with the clinical manifestations of MetS. Therefore, we selected parameters relative to both the glucose tolerance and lipid altered metabolism, but also oxidative pattern. We assessed some biomarkers of oxidative stress i.e., thiols balance, lipid peroxidation and antioxidant barriers, via the use of specific biochemical assays, individuating eventual cross correlation with parameters relative to MetS through a Principal Component Analysis (PCA). The present study shows that 8 weeks of HFD induce MetS in rats, altering glucose and lipid homeostasis and increasing visceral adipose tissue, but also impairing the physiological antioxidant responses that could not counteract the oxidative stress condition. Crucially, cross-correlation analysis suggested that the assessment of specific oxidative stress parameters reported here can provide information comparable to the more widely acquired biomarkers of Mets such as glucose tolerance. Lastly, hepatic steatosis in association with the oxidative stress condition was also highlighted by histological analysis. This research will elucidate the fundamental impact of these oxidative stress parameters on MetS induced in the HFD rat model, tracing paths for developing prevention approaches.
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Affiliation(s)
- Danila Di Majo
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy
- Postgraduate School of Nutrition and Food Science, University of Palermo, 90100 Palermo, Italy
| | - Pierangelo Sardo
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy
- Postgraduate School of Nutrition and Food Science, University of Palermo, 90100 Palermo, Italy
| | - Giuseppe Giglia
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy
- Euro Mediterranean Institute of Science and Technology, I.E.ME.S.T, 90139 Palermo, Italy
| | - Valentina Di Liberto
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy
| | - Francesco Paolo Zummo
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy
| | - Maria Grazia Zizzo
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, 90128 Palermo, Italy
- ATeN (Advanced Technologies Network) Center, Viale delle Scienze, 90128 Palermo, Italy
| | | | - Francesca Rappa
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy
| | - Giorgia Intili
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy
| | | | - Daniele Gallo
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy
| | - Giuseppe Ferraro
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy
- Postgraduate School of Nutrition and Food Science, University of Palermo, 90100 Palermo, Italy
| | - Giuditta Gambino
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy
- Correspondence: ; Tel./Fax: +39-09123865843
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24
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Attanzio A, Restivo I, Tutone M, Tesoriere L, Allegra M, Livrea MA. Redox Properties, Bioactivity and Health Effects of Indicaxanthin, a Bioavailable Phytochemical from Opuntia ficus indica, L.: A Critical Review of Accumulated Evidence and Perspectives. Antioxidants (Basel) 2022; 11:antiox11122364. [PMID: 36552572 PMCID: PMC9774763 DOI: 10.3390/antiox11122364] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 11/16/2022] [Accepted: 11/23/2022] [Indexed: 12/05/2022] Open
Abstract
Phytochemicals from plant foods are considered essential to human health. Known for their role in the adaptation of plants to their environment, these compounds can induce adaptive responses in cells, many of which are directed at maintaining the redox tone. Indicaxanthin is a long-known betalain pigment found in the genus Opuntia of cactus pear and highly concentrated in the edible fruits of O. ficus indica, L. whose bioactivity has been overlooked until recently. This review summarizes studies conducted so far in vitro and in vivo, most of which have been performed in our laboratory. The chemical and physicochemical characteristics of Indicaxanthin are reflected in the molecule's reducing properties and antioxidant effects and help explain its ability to interact with membranes, modulate redox-regulated cellular pathways, and possibly bind to protein molecules. Measurement of bioavailability in volunteers has been key to exploring its bioactivity; amounts consistent with dietary intake, or plasma concentration after dietary consumption of cactus pear fruit, have been used in experimental setups mimicking physiological or pathophysiological conditions, in cells and in animals, finally suggesting pharmacological potential and relevance of Indicaxanthin as a nutraceutical. In reporting experimental results, this review also aimed to raise questions and seek insights for further basic research and health promotion applications.
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25
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Cheng Z, Qiao D, Zhao S, Zhang B, Lin Q, Xie F. Whole grain rice: Updated understanding of starch digestibility and the regulation of glucose and lipid metabolism. Compr Rev Food Sci Food Saf 2022; 21:3244-3273. [PMID: 35686475 DOI: 10.1111/1541-4337.12985] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 04/18/2022] [Accepted: 05/03/2022] [Indexed: 11/27/2022]
Abstract
Nowadays, resulting from disordered glucose and lipid metabolism, metabolic diseases (e.g., hyperglycemia, type 2 diabetes, and obesity) are among the most serious health issues facing humans worldwide. Increasing evidence has confirmed that dietary intervention (with healthy foods) is effective at regulating the metabolic syndrome. Whole grain rice (WGR) rich in dietary fiber and many bioactive compounds (e.g., γ-amino butyric acid, γ-oryzanol, and polyphenols) can not only inhibit starch digestion and prevent rapid increase in the blood glucose level, but also reduce oxidative stress and damage to the liver, thereby regulating glucose and lipid metabolism. The rate of starch digestion is directly related to the blood glucose level in the organism after WGR intake. Therefore, the effects of different factors (e.g., additives, cooking, germination, and physical treatments) on WGR starch digestibility are examined in this review. In addition, the mechanisms from human and animal experiments regarding the correlation between the intake of WGR or its products and the lowered blood glucose and lipid levels and the reduced incidence of diabetes and obesity are discussed. Moreover, information on developing WGR products with the health benefits is provided.
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Affiliation(s)
- Zihang Cheng
- Group for Cereals and Oils Processing, College of Food Science and Technology, Key Laboratory of Environment Correlative Dietology (Ministry of Education), Huazhong Agricultural University, Wuhan, China
| | - Dongling Qiao
- Glyn O. Phillips Hydrocolloid Research Centre at HBUT, School of Food and Biological Engineering, Hubei University of Technology, Wuhan, China
| | - Siming Zhao
- Group for Cereals and Oils Processing, College of Food Science and Technology, Key Laboratory of Environment Correlative Dietology (Ministry of Education), Huazhong Agricultural University, Wuhan, China
| | - Binjia Zhang
- Group for Cereals and Oils Processing, College of Food Science and Technology, Key Laboratory of Environment Correlative Dietology (Ministry of Education), Huazhong Agricultural University, Wuhan, China
| | - Qinlu Lin
- National Engineering Laboratory for Rice and By-product Deep Processing, Central South University of Forestry and Technology, Changsha, China
| | - Fengwei Xie
- School of Engineering, Newcastle University, Newcastle upon Tyne, UK
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26
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Boonloh K, Thanaruksa R, Proongkhong T, Thawornchinsombut S, Pannangpetch P. Nil-Surin Rice Bran Hydrolysates Improve Lipid Metabolism and Hepatic Steatosis by Regulating Secretion of Adipokines and Expression of Lipid-Metabolism Genes. J Med Food 2022; 25:597-606. [PMID: 35708630 DOI: 10.1089/jmf.2021.k.0170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Overconsumption of a high caloric diet is associated with metabolic disorders and a heightened risk of diabetes mellitus (DM), hepatic steatosis, and cardiovascular complications. The use of functional food has received much attention as a strategy in the prevention and treatment of metabolic disorders. This present study investigated whether Nil-Surin rice bran hydrolysates (NRH) could prevent or ameliorate the progression of metabolic disorders in rats in which insulin resistance (IR) was induced by a high fat-high fructose diet (HFFD). After 10 weeks of the HFFD, the rats showed elevated fasting blood glucose (FBG), impaired glucose tolerance, dysregulation of adipokine secretion, distorted lipid metabolism such as dyslipidemia, and increased intrahepatic fat accumulation. The IR was significantly attenuated by a daily dose of NRH (100 or 300 mg/kg/day). Doses of NRH rectified adipokine dysregulation by increasing serum adiponectin and improving hyperleptinemia. Interestingly, NRH decreased intrahepatic fat accumulation and improved dyslipidemia as shown by decreased levels of hepatic triglyceride (TG) and serum TG, total cholesterol and low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol. In addition, a modulation of expression of lipid metabolism genes was observed: NRH prevented upregulation of the lipogenesis genes Srebf1 and Fasn. In addition, NRH enhanced the expression of fatty-acid oxidation genes, as evidenced by an increase of Ppara and Cpt1a when compared with the HFFD control group. The activities of NRH in the modulation of lipid metabolism and rectifying the dysregulation of adipokines may result in a decreased risk of DM and hepatic steatosis. Therefore, NRH may be beneficial in ameliorating metabolic disorders in the HFFD model.
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Affiliation(s)
- Kampeebhorn Boonloh
- Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Muang District, Thailand.,Cardiovascular Research Group, Khon Kaen University, Muang District, Thailand
| | - Ratthipha Thanaruksa
- Rice Department, Surin Rice Research Center, Agricultural and Cooperatives Ministry, Surin, Thailand
| | - Tunvaraporn Proongkhong
- Rice Department, Chum Phae Rice Research Center, Agricultural and Cooperatives Ministry, Khon Kaen, Thailand
| | - Supawan Thawornchinsombut
- Department of Food Technology, Faculty of Technology, Khon Kaen University, Muang District, Thailand
| | - Patchareewan Pannangpetch
- Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Muang District, Thailand.,Cardiovascular Research Group, Khon Kaen University, Muang District, Thailand
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27
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Gentile A, Magnacca N, de Matteis R, Moreno M, Cioffi F, Giacco A, Lanni A, de Lange P, Senese R, Goglia F, Silvestri E, Lombardi A. Ablation of uncoupling protein 3 affects interrelated factors leading to lipolysis and insulin resistance in visceral white adipose tissue. FASEB J 2022; 36:e22325. [PMID: 35452152 DOI: 10.1096/fj.202101816rr] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 04/08/2022] [Accepted: 04/11/2022] [Indexed: 11/11/2022]
Abstract
The physiological role played by uncoupling protein 3 (UCP3) in white adipose tissue (WAT) has not been elucidated so far. In the present study, we evaluated the impact of the absence of the whole body UCP3 on WAT physiology in terms of ability to store triglycerides, oxidative capacity, response to insulin, inflammation, and adipokine production. Wild type (WT) and UCP3 Knockout (KO) mice housed at thermoneutrality (30°C) have been used as the animal model. Visceral gonadic WAT (gWAT) from KO mice showed an impaired capacity to store triglycerides (TG) as indicated by its lowered weight, reduced adipocyte diameter, and higher glycerol release (index of lipolysis). The absence of UCP3 reduces the maximal oxidative capacity of gWAT, increases mitochondrial free radicals, and activates ER stress. These processes are associated with increased levels of monocyte chemoattractant protein-1 and TNF-α. The response of gWAT to in vivo insulin administration, revealed by (ser473)-AKT phosphorylation, was blunted in KO mice, with a putative role played by eif2a, JNK, and inflammation. Variations in adipokine levels in the absence of UCP3 were observed, including reduced adiponectin levels both in gWAT and serum. As a whole, these data indicate an important role of UCP3 in regulating the metabolic functionality of gWAT, with its absence leading to metabolic derangement. The obtained results help to clarify some aspects of the association between metabolic disorders and low UCP3 levels.
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Affiliation(s)
| | - Nunzia Magnacca
- Department of Biology, University of Naples Federico II, Naples, Italy
| | - Rita de Matteis
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy
| | - Maria Moreno
- Department of Science and Technology, University of Sannio, Benevento, Italy
| | - Federica Cioffi
- Department of Science and Technology, University of Sannio, Benevento, Italy
| | - Antonia Giacco
- Department of Science and Technology, University of Sannio, Benevento, Italy
| | - Antonia Lanni
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, Caserta, Italy
| | - Pieter de Lange
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, Caserta, Italy
| | - Rosalba Senese
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, Caserta, Italy
| | - Fernando Goglia
- Department of Science and Technology, University of Sannio, Benevento, Italy
| | - Elena Silvestri
- Department of Science and Technology, University of Sannio, Benevento, Italy
| | - Assunta Lombardi
- Department of Biology, University of Naples Federico II, Naples, Italy
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28
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Kim SQ, Mohallem R, Franco J, Buhman KK, Kim KH, Aryal UK. Multi-Omics Approach Reveals Dysregulation of Protein Phosphorylation Correlated with Lipid Metabolism in Mouse Non-Alcoholic Fatty Liver. Cells 2022; 11:cells11071172. [PMID: 35406736 PMCID: PMC8997945 DOI: 10.3390/cells11071172] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 03/24/2022] [Accepted: 03/26/2022] [Indexed: 02/04/2023] Open
Abstract
Obesity caused by overnutrition is a major risk factor for non-alcoholic fatty liver disease (NAFLD). Several lipid intermediates such as fatty acids, glycerophospholipids and sphingolipids are implicated in NAFLD, but detailed characterization of lipids and their functional links to proteome and phosphoproteome remain to be elucidated. To characterize this complex molecular relationship, we used a multi-omics approach by conducting comparative proteomic, phoshoproteomic and lipidomic analyses of high fat (HFD) and low fat (LFD) diet fed mice livers. We quantified 2447 proteins and 1339 phosphoproteins containing 1650 class I phosphosites, of which 669 phosphosites were significantly different between HFD and LFD mice livers. We detected alterations of proteins associated with cellular metabolic processes such as small molecule catabolic process, monocarboxylic acid, long- and medium-chain fatty acid, and ketone body metabolic processes, and peroxisome organization. We observed a significant downregulation of protein phosphorylation in HFD fed mice liver in general. Untargeted lipidomics identified upregulation of triacylglycerols, glycerolipids and ether glycerophosphocholines and downregulation of glycerophospholipids, such as lysoglycerophospholipids, as well as ceramides and acylcarnitines. Analysis of differentially regulated phosphosites revealed phosphorylation dependent deregulation of insulin signaling as well as lipogenic and lipolytic pathways during HFD induced obesity. Thus, this study reveals a molecular connection between decreased protein phosphorylation and lipolysis, as well as lipid-mediated signaling in diet-induced obesity.
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Affiliation(s)
- Sora Q. Kim
- Department of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA; (S.Q.K.); (K.K.B.)
| | - Rodrigo Mohallem
- Bindley Bioscience Center, Purdue Proteomics Facility, Purdue University, West Lafayette, IN 47907, USA; (R.M.); (J.F.)
- Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA
| | - Jackeline Franco
- Bindley Bioscience Center, Purdue Proteomics Facility, Purdue University, West Lafayette, IN 47907, USA; (R.M.); (J.F.)
| | - Kimberly K. Buhman
- Department of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA; (S.Q.K.); (K.K.B.)
| | - Kee-Hong Kim
- Department of Food Science, Purdue University, West Lafayette, IN 47907, USA;
| | - Uma K. Aryal
- Bindley Bioscience Center, Purdue Proteomics Facility, Purdue University, West Lafayette, IN 47907, USA; (R.M.); (J.F.)
- Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA
- Correspondence: ; Tel.: +1-765-494-4960
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29
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Dysmetabolism and Neurodegeneration: Trick or Treat? Nutrients 2022; 14:nu14071425. [PMID: 35406040 PMCID: PMC9003269 DOI: 10.3390/nu14071425] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 03/24/2022] [Accepted: 03/25/2022] [Indexed: 02/06/2023] Open
Abstract
Accumulating evidence suggests the existence of a strong link between metabolic syndrome and neurodegeneration. Indeed, epidemiologic studies have described solid associations between metabolic syndrome and neurodegeneration, whereas animal models contributed for the clarification of the mechanistic underlying the complex relationships between these conditions, having the development of an insulin resistance state a pivotal role in this relationship. Herein, we review in a concise manner the association between metabolic syndrome and neurodegeneration. We start by providing concepts regarding the role of insulin and insulin signaling pathways as well as the pathophysiological mechanisms that are in the genesis of metabolic diseases. Then, we focus on the role of insulin in the brain, with special attention to its function in the regulation of brain glucose metabolism, feeding, and cognition. Moreover, we extensively report on the association between neurodegeneration and metabolic diseases, with a particular emphasis on the evidence observed in animal models of dysmetabolism induced by hypercaloric diets. We also debate on strategies to prevent and/or delay neurodegeneration through the normalization of whole-body glucose homeostasis, particularly via the modulation of the carotid bodies, organs known to be key in connecting the periphery with the brain.
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30
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Gálvez I, Navarro MC, Martín-Cordero L, Otero E, Hinchado MD, Ortega E. The Influence of Obesity and Weight Loss on the Bioregulation of Innate/Inflammatory Responses: Macrophages and Immunometabolism. Nutrients 2022; 14:nu14030612. [PMID: 35276970 PMCID: PMC8840693 DOI: 10.3390/nu14030612] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 01/24/2022] [Accepted: 01/27/2022] [Indexed: 12/12/2022] Open
Abstract
Obesity is characterized by low-grade inflammation and more susceptibility to infection, particularly viral infections, as clearly demonstrated in COVID-19. In this context, immunometabolism and metabolic flexibility of macrophages play an important role. Since inflammation is an inherent part of the innate response, strategies for decreasing the inflammatory response must avoid immunocompromise the innate defenses against pathogen challenges. The concept “bioregulation of inflammatory/innate responses” was coined in the context of the effects of exercise on these responses, implying a reduction in excessive inflammatory response, together with the preservation or stimulation of the innate response, with good transitions between pro- and anti-inflammatory macrophages adapted to each individual’s inflammatory set-point in inflammatory diseases, particularly in obesity. The question now is whether these responses can be obtained in the context of weight loss by dietary interventions (low-fat diet or abandonment of the high-fat diet) in the absence of exercise, which can be especially relevant for obese individuals with difficulties exercising such as those suffering from persistent COVID-19. Results from recent studies are controversial and do not point to a clear anti-inflammatory effect of these dietary interventions, particularly in the adipose tissue. Further research focusing on the innate response is also necessary.
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Affiliation(s)
- Isabel Gálvez
- Immunophyisiology Research Group, Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 06071 Badajoz, Spain; (I.G.); (M.C.N.); (L.M.-C.); (E.O.); (M.D.H.)
- Immunophysiology Research Group, Nursing Department, Faculty of Medicine and Health Sciences, University of Extremadura, 06071 Badajoz, Spain
| | - María Carmen Navarro
- Immunophyisiology Research Group, Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 06071 Badajoz, Spain; (I.G.); (M.C.N.); (L.M.-C.); (E.O.); (M.D.H.)
- Immunophysiology Research Group, Physiology Department, Faculty of Sciences, University of Extremadura, 06071 Badajoz, Spain
| | - Leticia Martín-Cordero
- Immunophyisiology Research Group, Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 06071 Badajoz, Spain; (I.G.); (M.C.N.); (L.M.-C.); (E.O.); (M.D.H.)
- Immunophysiology Research Group, Nursing Department, University Center of Plasencia, University of Extremadura, 10600 Plasencia, Spain
| | - Eduardo Otero
- Immunophyisiology Research Group, Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 06071 Badajoz, Spain; (I.G.); (M.C.N.); (L.M.-C.); (E.O.); (M.D.H.)
- Immunophysiology Research Group, Physiology Department, Faculty of Sciences, University of Extremadura, 06071 Badajoz, Spain
| | - María Dolores Hinchado
- Immunophyisiology Research Group, Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 06071 Badajoz, Spain; (I.G.); (M.C.N.); (L.M.-C.); (E.O.); (M.D.H.)
- Immunophysiology Research Group, Physiology Department, Faculty of Sciences, University of Extremadura, 06071 Badajoz, Spain
| | - Eduardo Ortega
- Immunophyisiology Research Group, Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 06071 Badajoz, Spain; (I.G.); (M.C.N.); (L.M.-C.); (E.O.); (M.D.H.)
- Immunophysiology Research Group, Physiology Department, Faculty of Sciences, University of Extremadura, 06071 Badajoz, Spain
- Correspondence: ; Tel.: +34-924-289-300
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Guerreiro VA, Carvalho D, Freitas P. Obesity, Adipose Tissue, and Inflammation Answered in Questions. J Obes 2022; 2022:2252516. [PMID: 35321537 PMCID: PMC8938152 DOI: 10.1155/2022/2252516] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 12/19/2021] [Accepted: 01/03/2022] [Indexed: 12/27/2022] Open
Abstract
Background. Obesity is a global health problem of epidemic proportions, which is characterized by increased adipose tissue (AT) mass and significant repercussions in different body apparati and systems. AT is a special connective tissue, which contains several types of cells, in addition to adipocytes, and is a highly active endocrine and immune organ, which directly modulates many processes, including energy balance, metabolism, and inflammation. Summary. In this paper, the authors list and attempt to answer in a brief and simple way several questions regarding the complex relationships between obesity, adipose tissue, and inflammation, with the objective to provide an easy way to understand the main changes that occur in this pathological state. The questions are the following: Is adipose tissue only made up of adipocytes? Are adipocytes just a reservoir of free fatty acids? Do different types of fatty tissue exist? If so, which types? Can we further subcategorize the types of adipose tissue? Is it possible to form new adipocytes during adulthood? What is the role of inflammation? What is the role of macrophages? Are macrophages central mediators of obesity-induced adipose tissue inflammation and insulin resistance? What causes macrophage infiltration into adipose tissue? What is the role of hypoxia in AT alterations? Is there cross talk between adipocytes and immune cells? What other changes occur in AT in obesity? Does metabolically healthy obesity really exist? Is this a benign condition? Key messages. Obesity is a complex disease with numerous metabolic consequences, which are mainly the result of dysfunction that occurs in the adipose tissue of patients with this pathology. Understanding the pathophysiology of AT and the changes that occur in obesity would contribute to a better approach to patients with obesity, with the inherent medical implications that could result from this.
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Affiliation(s)
- Vanessa A. Guerreiro
- Department of Endocrinology Diabetes and Metabolism, Centro Hospitalar e Universitário de São João, Porto 4200-319, Portugal
- Faculty of Medicine, Universidade do Porto, Porto 4200-319, Portugal
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4200-135, Portugal
| | - Davide Carvalho
- Department of Endocrinology Diabetes and Metabolism, Centro Hospitalar e Universitário de São João, Porto 4200-319, Portugal
- Faculty of Medicine, Universidade do Porto, Porto 4200-319, Portugal
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4200-135, Portugal
| | - Paula Freitas
- Department of Endocrinology Diabetes and Metabolism, Centro Hospitalar e Universitário de São João, Porto 4200-319, Portugal
- Faculty of Medicine, Universidade do Porto, Porto 4200-319, Portugal
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4200-135, Portugal
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Indicaxanthin from Opuntia ficus-indica Fruit Ameliorates Glucose Dysmetabolism and Counteracts Insulin Resistance in High-Fat-Diet-Fed Mice. Antioxidants (Basel) 2021; 11:antiox11010080. [PMID: 35052584 PMCID: PMC8773302 DOI: 10.3390/antiox11010080] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 12/22/2021] [Accepted: 12/23/2021] [Indexed: 12/16/2022] Open
Abstract
Obesity-related dysmetabolic conditions are amongst the most common causes of death globally. Indicaxanthin, a bioavailable betalain pigment from Opuntia ficus-indica fruit, has been demonstrated to modulate redox-dependent signalling pathways, exerting significant anti-oxidative and anti-inflammatory effects in vitro and in vivo. In light of the strict interconnections between inflammation, oxidative stress and insulin resistance (IR), a nutritionally relevant dose of indicaxanthin has been evaluated in a high-fat diet (HFD) model of obesity-related IR. To this end, biochemical and histological analysis, oxidative stress and inflammation evaluations in liver and adipose tissue were carried out. Our results showed that indicaxanthin treatment significantly reduced body weight, daily food intake and visceral fat mass. Moreover, indicaxanthin administration induced remarkable, beneficial effects on HFD-induced glucose dysmetabolism, reducing fasting glycaemia and insulinaemia, improving glucose and insulin tolerance and restoring the HOMA index to physiological values. These effects were associated with a reduction in hepatic and adipose tissue oxidative stress and inflammation. A decrease in RONS, malondialdehyde and NO levels, in TNF-α, CCL-2 and F4-80 gene expression, in p65, p-JNK, COX-2 and i-NOS protein levels, in crown-like structures and hepatic inflammatory foci was, indeed, observed. The current findings encourage further clinical studies to confirm the effectiveness of indicaxanthin to prevent and treat obesity-related dysmetabolic conditions.
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Verdú E, Homs J, Boadas-Vaello P. Physiological Changes and Pathological Pain Associated with Sedentary Lifestyle-Induced Body Systems Fat Accumulation and Their Modulation by Physical Exercise. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:13333. [PMID: 34948944 PMCID: PMC8705491 DOI: 10.3390/ijerph182413333] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 12/02/2021] [Accepted: 12/10/2021] [Indexed: 12/11/2022]
Abstract
A sedentary lifestyle is associated with overweight/obesity, which involves excessive fat body accumulation, triggering structural and functional changes in tissues, organs, and body systems. Research shows that this fat accumulation is responsible for several comorbidities, including cardiovascular, gastrointestinal, and metabolic dysfunctions, as well as pathological pain behaviors. These health concerns are related to the crosstalk between adipose tissue and body systems, leading to pathophysiological changes to the latter. To deal with these health issues, it has been suggested that physical exercise may reverse part of these obesity-related pathologies by modulating the cross talk between the adipose tissue and body systems. In this context, this review was carried out to provide knowledge about (i) the structural and functional changes in tissues, organs, and body systems from accumulation of fat in obesity, emphasizing the crosstalk between fat and body tissues; (ii) the crosstalk between fat and body tissues triggering pain; and (iii) the effects of physical exercise on body tissues and organs in obese and non-obese subjects, and their impact on pathological pain. This information may help one to better understand this crosstalk and the factors involved, and it could be useful in designing more specific training interventions (according to the nature of the comorbidity).
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Affiliation(s)
- Enrique Verdú
- Research Group of Clinical Anatomy, Embryology and Neuroscience (NEOMA), Department of Medical Sciences, University of Girona, 17003 Girona, Spain;
| | - Judit Homs
- Research Group of Clinical Anatomy, Embryology and Neuroscience (NEOMA), Department of Medical Sciences, University of Girona, 17003 Girona, Spain;
- Department of Physical Therapy, EUSES-University of Girona, 17190 Salt, Spain
| | - Pere Boadas-Vaello
- Research Group of Clinical Anatomy, Embryology and Neuroscience (NEOMA), Department of Medical Sciences, University of Girona, 17003 Girona, Spain;
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Gallegos-Cabriales EC, Rodriguez-Ayala E, Laviada-Molina HA, Nava-Gonzalez EJ, Salinas-Osornio RA, Orozco L, Leal-Berumen I, Castillo-Pineda JC, Gonzalez-Lopez L, Escudero-Lourdes C, Cornejo-Barrera J, Escalante-Araiza F, Huerta-Avila EE, Buenfil-Rello FA, Peschard VG, Silva E, Veloz-Garza RA, Martinez-Hernandez A, Barajas-Olmos FM, Molina-Segui F, Gonzalez-Ramirez L, Arjona-Villicaña RD, Hernandez-Escalante VM, Gaytan-Saucedo JF, Vaquera Z, Acebo-Martinez M, Murillo-Ramirez A, Diaz-Tena SP, Figueroa-Nuñez B, Valencia-Rendon ME, Garzon-Zamora R, Viveros-Paredes JM, Valdovinos-Chavez SB, Comuzzie AG, Haack K, Thorsell AA, Han X, Cole SA, Bastarrachea RA. Replication of Integrative Data Analysis for Adipose Tissue Dysfunction, Low-Grade Inflammation, Postprandial Responses and OMICs Signatures in Symptom-Free Adults. BIOLOGY 2021; 10:1342. [PMID: 34943258 PMCID: PMC8698545 DOI: 10.3390/biology10121342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 12/11/2021] [Accepted: 12/12/2021] [Indexed: 11/16/2022]
Abstract
We previously reported preliminary characterization of adipose tissue (AT) dysfunction through the adiponectin/leptin ratio (ALR) and fasting/postprandial (F/P) gene expression in subcutaneous (SQ) adipose tissue (AT) biopsies obtained from participants in the GEMM study, a precision medicine research project. Here we present integrative data replication of previous findings from an increased number of GEMM symptom-free (SF) adults (N = 124) to improve characterization of early biomarkers for cardiovascular (CV)/immunometabolic risk in SF adults with AT dysfunction. We achieved this goal by taking advantage of the rich set of GEMM F/P 5 h time course data and three tissue samples collected at the same time and frequency on each adult participant (F/P blood, biopsies of SQAT and skeletal muscle (SKM)). We classified them with the presence/absence of AT dysfunction: low (<1) or high (>1) ALR. We also examined the presence of metabolically healthy (MH)/unhealthy (MUH) individuals through low-grade chronic subclinical inflammation (high sensitivity C-reactive protein (hsCRP)), whole body insulin sensitivity (Matsuda Index) and Metabolic Syndrome criteria in people with/without AT dysfunction. Molecular data directly measured from three tissues in a subset of participants allowed fine-scale multi-OMIC profiling of individual postprandial responses (RNA-seq in SKM and SQAT, miRNA from plasma exosomes and shotgun lipidomics in blood). Dynamic postprandial immunometabolic molecular endophenotypes were obtained to move towards a personalized, patient-defined medicine. This study offers an example of integrative translational research, which applies bench-to-bedside research to clinical medicine. Our F/P study design has the potential to characterize CV/immunometabolic early risk detection in support of precision medicine and discovery in SF individuals.
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Affiliation(s)
- Esther C. Gallegos-Cabriales
- Facultad de Enfermería, Universidad Autónoma de Nuevo León (UANL), Monterrey 64460, Mexico; (E.C.G.-C.); (R.A.V.-G.); (S.B.V.-C.)
| | - Ernesto Rodriguez-Ayala
- Centro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac Norte, Lomas Anahuac 52786, Mexico; (E.R.-A.); (F.E.-A.); (V.-G.P.); (E.S.)
| | - Hugo A. Laviada-Molina
- Escuela de Ciencias de la Salud, Universidad Marista de Mérida, Mérida 97300, Mexico; (H.A.L.-M.); (F.M.-S.); (L.G.-R.); (R.D.A.-V.); (V.M.H.-E.)
| | | | - Rocío A. Salinas-Osornio
- Departamento de Nutrición, Universidad del Valle de Atemajac (UNIVA), Zapopan 45050, Mexico; (R.A.S.-O.); (L.G.-L.); (M.E.V.-R.); (R.G.-Z.); (J.M.V.-P.)
| | - Lorena Orozco
- Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, SS, Ciudad de México 14610, Mexico; (L.O.); (E.E.H.-A.); (A.M.-H.); (F.M.B.-O.)
| | - Irene Leal-Berumen
- Facultad de Medicina y Ciencias Biomédicas, Universidad Autónoma de Chihuahua, Chihuahua 31125, Mexico;
| | - Juan Carlos Castillo-Pineda
- Departamento de Nutrición Humana, Universidad Latina de América, Morelia 58170, Mexico; (J.C.C.-P.); (A.M.-R.); (S.P.D.-T.)
| | - Laura Gonzalez-Lopez
- Departamento de Nutrición, Universidad del Valle de Atemajac (UNIVA), Zapopan 45050, Mexico; (R.A.S.-O.); (L.G.-L.); (M.E.V.-R.); (R.G.-Z.); (J.M.V.-P.)
| | - Claudia Escudero-Lourdes
- Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosi 78240, Mexico; (C.E.-L.); (M.A.-M.)
| | - Judith Cornejo-Barrera
- Departamento de Enseñanza, Postgrado e Investigación, Hospital Infantil de Tamaulipas, Ciudad Victoria 87150, Mexico;
| | - Fabiola Escalante-Araiza
- Centro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac Norte, Lomas Anahuac 52786, Mexico; (E.R.-A.); (F.E.-A.); (V.-G.P.); (E.S.)
- Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, SS, Ciudad de México 14610, Mexico; (L.O.); (E.E.H.-A.); (A.M.-H.); (F.M.B.-O.)
| | - Eira E. Huerta-Avila
- Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, SS, Ciudad de México 14610, Mexico; (L.O.); (E.E.H.-A.); (A.M.-H.); (F.M.B.-O.)
| | - Fatima A. Buenfil-Rello
- Population Health Program, Southwest National Primate Research Center (SNPRC), Texas Biomedical Research Institute, San Antonio, TX 78227-0549, USA; (F.A.B.-R.); (J.F.G.-S.); (Z.V.); (K.H.); (S.A.C.)
| | - Vanessa-Giselle Peschard
- Centro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac Norte, Lomas Anahuac 52786, Mexico; (E.R.-A.); (F.E.-A.); (V.-G.P.); (E.S.)
| | - Eliud Silva
- Centro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac Norte, Lomas Anahuac 52786, Mexico; (E.R.-A.); (F.E.-A.); (V.-G.P.); (E.S.)
| | - Rosa A. Veloz-Garza
- Facultad de Enfermería, Universidad Autónoma de Nuevo León (UANL), Monterrey 64460, Mexico; (E.C.G.-C.); (R.A.V.-G.); (S.B.V.-C.)
| | - Angelica Martinez-Hernandez
- Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, SS, Ciudad de México 14610, Mexico; (L.O.); (E.E.H.-A.); (A.M.-H.); (F.M.B.-O.)
| | - Francisco M. Barajas-Olmos
- Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, SS, Ciudad de México 14610, Mexico; (L.O.); (E.E.H.-A.); (A.M.-H.); (F.M.B.-O.)
| | - Fernanda Molina-Segui
- Escuela de Ciencias de la Salud, Universidad Marista de Mérida, Mérida 97300, Mexico; (H.A.L.-M.); (F.M.-S.); (L.G.-R.); (R.D.A.-V.); (V.M.H.-E.)
| | - Lucia Gonzalez-Ramirez
- Escuela de Ciencias de la Salud, Universidad Marista de Mérida, Mérida 97300, Mexico; (H.A.L.-M.); (F.M.-S.); (L.G.-R.); (R.D.A.-V.); (V.M.H.-E.)
| | - Ruy D. Arjona-Villicaña
- Escuela de Ciencias de la Salud, Universidad Marista de Mérida, Mérida 97300, Mexico; (H.A.L.-M.); (F.M.-S.); (L.G.-R.); (R.D.A.-V.); (V.M.H.-E.)
| | - Victor M. Hernandez-Escalante
- Escuela de Ciencias de la Salud, Universidad Marista de Mérida, Mérida 97300, Mexico; (H.A.L.-M.); (F.M.-S.); (L.G.-R.); (R.D.A.-V.); (V.M.H.-E.)
| | - Janeth F. Gaytan-Saucedo
- Population Health Program, Southwest National Primate Research Center (SNPRC), Texas Biomedical Research Institute, San Antonio, TX 78227-0549, USA; (F.A.B.-R.); (J.F.G.-S.); (Z.V.); (K.H.); (S.A.C.)
| | - Zoila Vaquera
- Population Health Program, Southwest National Primate Research Center (SNPRC), Texas Biomedical Research Institute, San Antonio, TX 78227-0549, USA; (F.A.B.-R.); (J.F.G.-S.); (Z.V.); (K.H.); (S.A.C.)
| | - Monica Acebo-Martinez
- Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosi 78240, Mexico; (C.E.-L.); (M.A.-M.)
| | - Areli Murillo-Ramirez
- Departamento de Nutrición Humana, Universidad Latina de América, Morelia 58170, Mexico; (J.C.C.-P.); (A.M.-R.); (S.P.D.-T.)
| | - Sara P. Diaz-Tena
- Departamento de Nutrición Humana, Universidad Latina de América, Morelia 58170, Mexico; (J.C.C.-P.); (A.M.-R.); (S.P.D.-T.)
| | - Benigno Figueroa-Nuñez
- Clínica de Enfermedades Crónicas y Procedimientos Especiales (CECYPE), Morelia 58249, Mexico;
| | - Melesio E. Valencia-Rendon
- Departamento de Nutrición, Universidad del Valle de Atemajac (UNIVA), Zapopan 45050, Mexico; (R.A.S.-O.); (L.G.-L.); (M.E.V.-R.); (R.G.-Z.); (J.M.V.-P.)
| | - Rafael Garzon-Zamora
- Departamento de Nutrición, Universidad del Valle de Atemajac (UNIVA), Zapopan 45050, Mexico; (R.A.S.-O.); (L.G.-L.); (M.E.V.-R.); (R.G.-Z.); (J.M.V.-P.)
| | - Juan Manuel Viveros-Paredes
- Departamento de Nutrición, Universidad del Valle de Atemajac (UNIVA), Zapopan 45050, Mexico; (R.A.S.-O.); (L.G.-L.); (M.E.V.-R.); (R.G.-Z.); (J.M.V.-P.)
| | - Salvador B. Valdovinos-Chavez
- Facultad de Enfermería, Universidad Autónoma de Nuevo León (UANL), Monterrey 64460, Mexico; (E.C.G.-C.); (R.A.V.-G.); (S.B.V.-C.)
| | | | - Karin Haack
- Population Health Program, Southwest National Primate Research Center (SNPRC), Texas Biomedical Research Institute, San Antonio, TX 78227-0549, USA; (F.A.B.-R.); (J.F.G.-S.); (Z.V.); (K.H.); (S.A.C.)
| | | | - Xianlin Han
- Department of Medicine, Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health San Antonio, San Antonio, TX 78229, USA;
| | - Shelley A. Cole
- Population Health Program, Southwest National Primate Research Center (SNPRC), Texas Biomedical Research Institute, San Antonio, TX 78227-0549, USA; (F.A.B.-R.); (J.F.G.-S.); (Z.V.); (K.H.); (S.A.C.)
| | - Raul A. Bastarrachea
- Population Health Program, Southwest National Primate Research Center (SNPRC), Texas Biomedical Research Institute, San Antonio, TX 78227-0549, USA; (F.A.B.-R.); (J.F.G.-S.); (Z.V.); (K.H.); (S.A.C.)
- Sansum Diabetes Research Institute, Santa Barbara, CA 93105, USA;
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Vitamin D Deficiency Is Inversely Associated with Homeostatic Model Assessment of Insulin Resistance. Nutrients 2021; 13:nu13124358. [PMID: 34959910 PMCID: PMC8705502 DOI: 10.3390/nu13124358] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 11/24/2021] [Accepted: 11/25/2021] [Indexed: 01/08/2023] Open
Abstract
The study was conducted to comprehensively assess the association of the concentration of vitamin D in the blood and insulin resistance in non-diabetic subjects. The objective was to pool the results from all observational studies from the beginning of 1980 to August 2021. PubMed, Medline and Embase were systematically searched for the observational studies. Filters were used for more focused results. A total of 2248 articles were found after raw search which were narrowed down to 32 articles by the systematic selection of related articles. Homeostatic Model Assessment of Insulin Resistance (HOMAIR) was used as the measure of insulin resistance and correlation coefficient was used as a measure of the relationship between vitamin D levels and the insulin resistance. Risk of bias tables and summary plots were built using Revman software version 5.3 while Comprehensive meta-analysis version 3 was used for the construction of forest plot. The results showed an inverse association between the status of vitamin D and insulin resistance (r = -0.217; 95% CI = -0.161 to -0.272; p = 0.000). A supplement of vitamin D can help reduce the risk of insulin resistance; however further studies, like randomized controlled trials are needed to confirm the results.
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Arora A, Behl T, Sehgal A, Singh S, Sharma N, Chigurupati S, Kaur R, Bhatia S, Al-Harrasi A, Vargas-De-La-Cruz C, Bungau S. Free fatty acid receptor 1: a ray of hope in the therapy of type 2 diabetes mellitus. Inflammopharmacology 2021; 29:1625-1639. [PMID: 34669065 DOI: 10.1007/s10787-021-00879-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Accepted: 09/21/2021] [Indexed: 12/25/2022]
Abstract
Free fatty acid receptor 1 (FFAR1) is a G-protein coupled receptor with prominent expression on pancreatic beta cells, bones, intestinal cells as well as the nerve cells. This receptor mediates a multitude of functions in the body including release of incretins, secretion of insulin as well as sensation of pain. Since FFAR1 causes secretion of insulin and regulates glucose metabolism, efforts were made to unfold its structure followed by discovering agonists for the receptor and the utilization of these agonists in the therapy of type 2 diabetes mellitus. Development of such functional FFAR1 agonists is a necessity because the currently available therapy for type 2 diabetes mellitus has numerous drawbacks, of which, the major one is hypoglycemia. Since the most prominent effect of the FFAR1 agonists is on glucose concentration in the body, so the major research is focused on treating type 2 diabetes mellitus, though the agonists could benefit other metabolic disorders and neurological disorders as well. The agonists developed so far had one major limitation, i.e., hepatotoxicity. Although, the only agonist that could reach phase 3 clinical trials was TAK-875 developed by Takeda Pharmaceuticals but it was also withdrawn due to toxic effects on the liver. Thus, there are numerous agonists for the varied binding sites of the receptor but no drug available yet. There does seem to be a ray of hope in the drugs that target FFAR1 but a lot more efforts towards drug discovery would result in the successful management of type 2 diabetes mellitus.
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Affiliation(s)
- Arpita Arora
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Tapan Behl
- Chitkara College of Pharmacy, Chitkara University, Punjab, India.
| | - Aayush Sehgal
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Sukhbir Singh
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Neelam Sharma
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Sridevi Chigurupati
- Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraidah, Kingdom of Saudi Arabia
| | - Rajwinder Kaur
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Saurabh Bhatia
- Natural and Medical Sciences Research Centre, University of Nizwa, Nizwa, Oman
- School of Health Science, University of Petroleum and Energy Studies, Dehradun, Uttarakhand, India
| | - Ahmed Al-Harrasi
- Natural and Medical Sciences Research Centre, University of Nizwa, Nizwa, Oman
| | - Celia Vargas-De-La-Cruz
- Faculty of Pharmacy and Biochemistry, Academic Department of Pharmacology, Bromatology and Toxicology, Centro Latinoamericano de Ensenanza e Investigacion en Bacteriologia Alimentaria, Universidad Nacional Mayor de San Marcos, Lima, Peru
- E-Health Research Center, Universidad de Ciencias y Humanidades, Lima, Peru
| | - Simona Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania
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Dose- and Time-Dependent Effects of Oleate on Mitochondrial Fusion/Fission Proteins and Cell Viability in HepG2 Cells: Comparison with Palmitate Effects. Int J Mol Sci 2021; 22:ijms22189812. [PMID: 34575980 PMCID: PMC8468319 DOI: 10.3390/ijms22189812] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 09/07/2021] [Indexed: 12/31/2022] Open
Abstract
Mitochondrial impairments in dynamic behavior (fusion/fission balance) associated with mitochondrial dysfunction play a key role in cell lipotoxicity and lipid-induced metabolic diseases. The present work aimed to evaluate dose- and time-dependent effects of the monounsaturated fatty acid oleate on mitochondrial fusion/fission proteins in comparison with the saturated fatty acid palmitate in hepatic cells. To this end, HepG-2 cells were treated with 0, 10 μM, 50 μM, 100 μM, 250 μM or 500 μM of either oleate or palmitate for 8 or 24 h. Cell viability and lipid accumulation were evaluated to assess lipotoxicity. Mitochondrial markers of fusion (mitofusin 2, MFN2) and fission (dynamin-related protein 1, DRP1) processes were evaluated by Western blot analysis. After 8 h, the highest dose of oleate induced a decrease in DRP1 content without changes in MFN2 content in association with cell viability maintenance, whereas palmitate induced a decrease in cell viability associated with a decrease mainly in MFN2 content. After 24 h, oleate induced MFN2 increase, whereas palmitate induced DRP1 increase associated with a higher decrease in cell viability with high doses compared to oleate. This finding could be useful to understand the role of mitochondria in the protective effects of oleate as a bioactive compound.
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Cimmino F, Catapano A, Trinchese G, Cavaliere G, Culurciello R, Fogliano C, Penna E, Lucci V, Crispino M, Avallone B, Pizzo E, Mollica MP. Dietary Micronutrient Management to Treat Mitochondrial Dysfunction in Diet-Induced Obese Mice. Int J Mol Sci 2021; 22:2862. [PMID: 33799812 PMCID: PMC8000238 DOI: 10.3390/ijms22062862] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 02/25/2021] [Accepted: 03/08/2021] [Indexed: 02/04/2023] Open
Abstract
Obesity and associated metabolic disturbances, which have been increasing worldwide in recent years, are the consequences of unhealthy diets and physical inactivity and are the main factors underlying non-communicable diseases (NCD). These diseases are now responsible for about three out of five deaths worldwide, and it has been shown that they depend on mitochondrial dysfunction, systemic inflammation and oxidative stress. It was also demonstrated that several nutritional components modulating these processes are able to influence metabolic homeostasis and, consequently, to prevent or delay the onset of NCD. An interesting combination of nutraceutical substances, named DMG-gold, has been shown to promote metabolic and physical wellness. The aim of this research was to investigate the metabolic, inflammatory and oxidative pathways modulated by DMG-gold in an animal model with diet-induced obesity. Our data indicate that DMG-gold decreases the metabolic efficiency and inflammatory state and acts as an antioxidant and detoxifying agent, modulating mitochondrial functions. Therefore, DMG-gold is a promising candidate in the prevention/treatment of NCD.
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Affiliation(s)
- Fabiano Cimmino
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy; (F.C.); (A.C.); (G.T.); (G.C.); (R.C.); (C.F.); (E.P.); (V.L.); (M.C.); (B.A.); (E.P.)
| | - Angela Catapano
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy; (F.C.); (A.C.); (G.T.); (G.C.); (R.C.); (C.F.); (E.P.); (V.L.); (M.C.); (B.A.); (E.P.)
- Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy
| | - Giovanna Trinchese
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy; (F.C.); (A.C.); (G.T.); (G.C.); (R.C.); (C.F.); (E.P.); (V.L.); (M.C.); (B.A.); (E.P.)
| | - Gina Cavaliere
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy; (F.C.); (A.C.); (G.T.); (G.C.); (R.C.); (C.F.); (E.P.); (V.L.); (M.C.); (B.A.); (E.P.)
| | - Rosanna Culurciello
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy; (F.C.); (A.C.); (G.T.); (G.C.); (R.C.); (C.F.); (E.P.); (V.L.); (M.C.); (B.A.); (E.P.)
| | - Chiara Fogliano
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy; (F.C.); (A.C.); (G.T.); (G.C.); (R.C.); (C.F.); (E.P.); (V.L.); (M.C.); (B.A.); (E.P.)
| | - Eduardo Penna
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy; (F.C.); (A.C.); (G.T.); (G.C.); (R.C.); (C.F.); (E.P.); (V.L.); (M.C.); (B.A.); (E.P.)
| | - Valeria Lucci
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy; (F.C.); (A.C.); (G.T.); (G.C.); (R.C.); (C.F.); (E.P.); (V.L.); (M.C.); (B.A.); (E.P.)
- IEOS, Institute of Experimental Endocrinology and Oncology “G. Salvatore”—National Research Council, 80131 Naples, Italy
| | - Marianna Crispino
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy; (F.C.); (A.C.); (G.T.); (G.C.); (R.C.); (C.F.); (E.P.); (V.L.); (M.C.); (B.A.); (E.P.)
| | - Bice Avallone
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy; (F.C.); (A.C.); (G.T.); (G.C.); (R.C.); (C.F.); (E.P.); (V.L.); (M.C.); (B.A.); (E.P.)
| | - Elio Pizzo
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy; (F.C.); (A.C.); (G.T.); (G.C.); (R.C.); (C.F.); (E.P.); (V.L.); (M.C.); (B.A.); (E.P.)
| | - Maria Pina Mollica
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy; (F.C.); (A.C.); (G.T.); (G.C.); (R.C.); (C.F.); (E.P.); (V.L.); (M.C.); (B.A.); (E.P.)
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Restivo I, Attanzio A, Tesoriere L, Allegra M. Suicidal Erythrocyte Death in Metabolic Syndrome. Antioxidants (Basel) 2021; 10:antiox10020154. [PMID: 33494379 PMCID: PMC7911029 DOI: 10.3390/antiox10020154] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 01/15/2021] [Accepted: 01/18/2021] [Indexed: 02/07/2023] Open
Abstract
Eryptosis is a coordinated, programmed cell death culminating with the disposal of cells without disruption of the cell membrane and the release of endocellular oxidative and pro-inflammatory milieu. While providing a convenient form of death for erythrocytes, dysregulated eryptosis may result in a series of detrimental and harmful pathological consequences highly related to the endothelial dysfunction (ED). Metabolic syndrome (MetS) is described as a cluster of cardiometabolic factors (hyperglycemia, dyslipidemia, hypertension and obesity) that increases the risk of cardiovascular complications such as those related to diabetes and atherosclerosis. In the light of the crucial role exerted by the eryptotic process in the ED, the focus of the present review is to report and discuss the involvement of eryptosis within MetS, where vascular complications are utterly relevant. Current knowledge on the mechanisms leading to eryptosis in MetS-related conditions (hyperglycemia, dyslipidemia, hypertension and obesity) will be analyzed. Moreover, clinical evidence supporting or proposing a role for eryptosis in the ED, associated to MetS cardiovascular complications, will be discussed.
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Affiliation(s)
| | | | - Luisa Tesoriere
- Correspondence: (L.T.); (M.A.); Tel.: +39-091-238-96803 (L.T. & M.A.)
| | - Mario Allegra
- Correspondence: (L.T.); (M.A.); Tel.: +39-091-238-96803 (L.T. & M.A.)
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Rodriguez-Ayala E, Gallegos-Cabrales EC, Gonzalez-Lopez L, Laviada-Molina HA, Salinas-Osornio RA, Nava-Gonzalez EJ, Leal-Berumen I, Escudero-Lourdes C, Escalante-Araiza F, Buenfil-Rello FA, Peschard VG, Laviada-Nagel A, Silva E, Veloz-Garza RA, Martinez-Hernandez A, Barajas-Olmos FM, Molina-Segui F, Gonzalez-Ramirez L, Espadas-Olivera R, Lopez-Muñoz R, Arjona-Villicaña RD, Hernandez-Escalante VM, Rodriguez-Arellano ME, Gaytan-Saucedo JF, Vaquera Z, Acebo-Martinez M, Cornejo-Barrera J, Jancy Andrea HQ, Castillo-Pineda JC, Murillo-Ramirez A, Diaz-Tena SP, Figueroa-Nuñez B, Valencia-Rendon ME, Garzon-Zamora R, Viveros-Paredes JM, Ángeles-Chimal J, Santa-Olalla Tapia J, Remes-Troche JM, Valdovinos-Chavez SB, Huerta-Avila EE, Lopez-Alvarenga JC, Comuzzie AG, Haack K, Han X, Orozco L, Weintraub S, Kent JW, Cole SA, Bastarrachea RA. Towards precision medicine: defining and characterizing adipose tissue dysfunction to identify early immunometabolic risk in symptom-free adults from the GEMM family study. Adipocyte 2020; 9:153-169. [PMID: 32272872 PMCID: PMC7153654 DOI: 10.1080/21623945.2020.1743116] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 03/03/2020] [Accepted: 03/10/2020] [Indexed: 12/15/2022] Open
Abstract
Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers. A relevant pattern of negative associations between decreased ALR and markers of systemic low-grade metaflammation, HOMA, and postprandial cardiovascular risk hyperinsulinemic, triglyceride and GLP-1 curves was found. We also analysed their plasma non-coding microRNAs and shotgun lipidomics profiles finding trends that may reflect a pattern of adipose tissue dysfunction in the fed and fasted state. Direct gene differential expression data showed initial patterns of AT molecular signatures of key immunometabolic genes involved in AT expansion, angiogenic remodelling and immune cell migration. These data reinforce the central, early role of AT dysfunction at the molecular and systemic level in the pathogenesis of IR and immunometabolic disorders.
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Affiliation(s)
- Ernesto Rodriguez-Ayala
- Centro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac Norte, México City, México
| | | | - Laura Gonzalez-Lopez
- Dirección de Postgrado e Investigación, Universidad del Valle de Atemajac (UNIVA), Zapopan, México
| | | | - Rocio A. Salinas-Osornio
- Dirección de Postgrado e Investigación, Universidad del Valle de Atemajac (UNIVA), Zapopan, México
| | | | - Irene Leal-Berumen
- Facultad de Medicina y Ciencias Biomédicas, Universidad Autónoma de Chihuahua, México
| | | | - Fabiola Escalante-Araiza
- Centro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac Norte, México City, México
| | - Fatima A. Buenfil-Rello
- Population Health Program, Texas Biomedical Research Institute and Southwest National Primate Research Center (SNPRC), San Antonio, TX, USA
| | - Vanessa-Giselle Peschard
- Centro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac Norte, México City, México
| | - Antonio Laviada-Nagel
- Population Health Program, Texas Biomedical Research Institute and Southwest National Primate Research Center (SNPRC), San Antonio, TX, USA
| | - Eliud Silva
- Centro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac Norte, México City, México
| | - Rosa A. Veloz-Garza
- Facultad de Enfermería, Universidad Autónoma de Nuevo León (UANL), Monterrey, México
| | - Angelica Martinez-Hernandez
- Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, México City, México
| | - Francisco M. Barajas-Olmos
- Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, México City, México
| | | | | | | | - Ricardo Lopez-Muñoz
- Escuela de Ciencias de la Salud, Universidad Marista de Mérida, Yucatán, Mexico
| | | | - Victor M. Hernandez-Escalante
- Population Health Program, Texas Biomedical Research Institute and Southwest National Primate Research Center (SNPRC), San Antonio, TX, USA
| | | | - Janeth F. Gaytan-Saucedo
- Population Health Program, Texas Biomedical Research Institute and Southwest National Primate Research Center (SNPRC), San Antonio, TX, USA
| | - Zoila Vaquera
- Population Health Program, Texas Biomedical Research Institute and Southwest National Primate Research Center (SNPRC), San Antonio, TX, USA
| | | | - Judith Cornejo-Barrera
- Departamento de Enseñanza, Postgrado e Investigación, Hospital Infantil de Tamaulipas, Ciudad, México
| | - Huertas-Quintero Jancy Andrea
- Population Health Program, Texas Biomedical Research Institute and Southwest National Primate Research Center (SNPRC), San Antonio, TX, USA
| | | | | | - Sara P. Diaz-Tena
- Departamento de Nutrición Humana, Universidad Latina de América, Morelia, México
| | | | | | - Rafael Garzon-Zamora
- Dirección de Postgrado e Investigación, Universidad del Valle de Atemajac (UNIVA), Zapopan, México
| | | | - José Ángeles-Chimal
- Facultad de Medicina, Universidad Autónoma Estado de Morelos, Cuernavaca, México
| | | | - José M. Remes-Troche
- Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, México
| | | | - Eira E. Huerta-Avila
- Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, México City, México
| | - Juan Carlos Lopez-Alvarenga
- School of Medicine & South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Edinburg, TX, USA
| | | | - Karin Haack
- Population Health Program, Texas Biomedical Research Institute and Southwest National Primate Research Center (SNPRC), San Antonio, TX, USA
| | - Xianlin Han
- Department of Medicine, Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health San Antonio, San Antonio, TX, USA
| | - Lorena Orozco
- Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, México City, México
| | - Susan Weintraub
- Department of Biochemistry, University of Texas Health Science Center, San Antonio, TX, USA
| | - Jack W. Kent
- Population Health Program, Texas Biomedical Research Institute and Southwest National Primate Research Center (SNPRC), San Antonio, TX, USA
| | - Shelley A. Cole
- Population Health Program, Texas Biomedical Research Institute and Southwest National Primate Research Center (SNPRC), San Antonio, TX, USA
| | - Raul A. Bastarrachea
- Population Health Program, Texas Biomedical Research Institute and Southwest National Primate Research Center (SNPRC), San Antonio, TX, USA
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Bovolini A, Garcia J, Andrade MA, Duarte JA. Metabolic Syndrome Pathophysiology and Predisposing Factors. Int J Sports Med 2020; 42:199-214. [PMID: 33075830 DOI: 10.1055/a-1263-0898] [Citation(s) in RCA: 175] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors with high prevalence among adult populations and elevated costs for public health systems worldwide. Despite the lack of consensus regarding the syndrome definition and diagnosis criteria, it is characterized by the coexistence of risk factors such as abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, a prothrombotic and pro-inflammatory state, insulin resistance (IR), and higher glucose levels, factors indubitably linked to an increased risk of developing chronic conditions, such as type 2 diabetes (T2D) and cardiovascular disease (CVD). The syndrome has a complex and multifaceted origin not fully understood; however, it has been strongly suggested that sedentarism and unbalanced dietary patterns might play a fundamental role in its development. The purpose of this review is to provide an overview from the syndrome epidemiology, costs, and main etiological traits from its relationship with unhealthy diet patterns and sedentary lifestyles.
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Affiliation(s)
| | - Juliana Garcia
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences, University of Trás-os-Montes and Alto Douro, Vila Real
| | | | - José Alberto Duarte
- CIAFEL Faculty of Sport, University of Porto, Porto.,University Institute of Health Sciences (IUCS), Rua Central de Gandra, 1317 4585-116 Gandra Paredes, Portugal
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Interplay between Peripheral and Central Inflammation in Obesity-Promoted Disorders: The Impact on Synaptic Mitochondrial Functions. Int J Mol Sci 2020; 21:ijms21175964. [PMID: 32825115 PMCID: PMC7504224 DOI: 10.3390/ijms21175964] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Revised: 08/12/2020] [Accepted: 08/17/2020] [Indexed: 12/14/2022] Open
Abstract
The metabolic dysfunctions induced by high fat diet (HFD) consumption are not limited to organs involved in energy metabolism but cause also a chronic low-grade systemic inflammation that affects the whole body including the central nervous system. The brain has been considered for a long time to be protected from systemic inflammation by the blood–brain barrier, but more recent data indicated an association between obesity and neurodegeneration. Moreover, obesity-related consequences, such as insulin and leptin resistance, mitochondrial dysfunction and reactive oxygen species (ROS) production, may anticipate and accelerate the physiological aging processes characterized by systemic inflammation and higher susceptibility to neurological disorders. Here, we discussed the link between obesity-related metabolic dysfunctions and neuroinflammation, with particular attention to molecules regulating the interplay between energetic impairment and altered synaptic plasticity, for instance AMP-activated protein kinase (AMPK) and Brain-derived neurotrophic factor (BDNF). The effects of HFD-induced neuroinflammation on neuronal plasticity may be mediated by altered brain mitochondrial functions. Since mitochondria play a key role in synaptic areas, providing energy to support synaptic plasticity and controlling ROS production, the negative effects of HFD may be more pronounced in synapses. In conclusion, it will be emphasized how HFD-induced metabolic alterations, systemic inflammation, oxidative stress, neuroinflammation and impaired brain plasticity are tightly interconnected processes, implicated in the pathogenesis of neurological diseases.
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Kumar V, Sachan R, Rahman M, Sharma K, Al-Abbasi FA, Anwar F. Prunus amygdalus extract exert antidiabetic effect via inhibition of DPP-IV: in-silico and in-vivo approaches. J Biomol Struct Dyn 2020; 39:4160-4174. [PMID: 32602806 DOI: 10.1080/07391102.2020.1775124] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Prunus amygdalus (PA) is a popular invasive seed utilized in the management of diabetes in Jammu and Kashmir, India. The objective of the current study was to scrutinize the antidiabetic effect of Prunus amygdalus (PA) against Streptozotocin (STZ) induced diabetic rats and explore the possible mechanism of action at cellular and sub-cellular levels. Box Benkan Design (BBD) was performed to determine the effect of PA powder to methanol, extraction time and extraction temperature on DPPH and ABTS free radical scavenging activity of decoction. In-silico study was performed on GLUT1 (5EQG) and dipeptidyl peptidase IV (DPPIV) (2G63) protein. Type II diabetes mellitus was initiated by single intra-peritoneal injection of STZ. The Blood Glucose Level (BGL) and body weight were estimated at regular interval of time. The different biochemical parameters such as hepatic, antioxidant, and lipid parameters were estimated. At end of the study, pancreas was used for histopathological observation. The variation in DPPH antiradical scavenging activity 40.0-90.0% and ABTS antiradical scavenging activity 34-82%, were estimated respectively. STZ induced DM rats showed increased BGL at end of the experimental study. PA treatment significantly (p < 0.001) down-regulated the BGL level. PA significantly (p < 0.001) altered the biochemical, hepatic and antioxidant parameters in a dose-dependent manner. Histopathological examination demonstrated the constructive mass of β-cells in pancreas. Overall, the current study indicates that the PA treatment down-regulated the hyperglycemic, oxidative stress and hyperlipidaemia in diabetic rats, due to inhibition of enzymes or amelioration of oxidative stress. [Formula: see text] Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Vikas Kumar
- Natural Product Drug Discovery Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom Institute of Agriculture, Technology & Sciences, Allahabad, Uttar Pradesh, India
| | - Richa Sachan
- School of Pharmacy, Sungkyunkwan University, Seobu-ro, Jangan-gu, Suwon, Korea
| | - Mahfoozur Rahman
- Faculty of Health Sciences, Department of Pharmaceutical Sciences, Sam Higginbottom Institute of Agriculture, Technology & Sciences, Allahabad, Uttar Pradesh, India
| | - Kalicharan Sharma
- Faculty of Pharmacy, Department of Pharmaceutical Chemistry, SPER, Jamia Hamdard, New Delhi, India
| | - Fahad A Al-Abbasi
- Faculty of Science, Department of Biochemistry, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Firoz Anwar
- Faculty of Science, Department of Biochemistry, King Abdulaziz University, Jeddah, Saudi Arabia
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Albakheet SS, Yoon H, Shin HJ, Koh H, Kim S, Lee MJ. Bone marrow fat change in pediatric patients with non-alcoholic fatty liver disease. PLoS One 2020; 15:e0234096. [PMID: 32484830 PMCID: PMC7266329 DOI: 10.1371/journal.pone.0234096] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Accepted: 05/18/2020] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVES To investigate changes of fat in bone marrow (BM) and paraspinal muscle (PSM) associated with the degree of fatty liver in pediatric patients with non-alcoholic fatty liver disease (NAFLD) in consideration of age and body mass index (BMI). METHODS Hepatic fat, BM fat, and PSM fat from proton density fat fraction of liver MRI between June 2015 and April 2019 were quantitatively evaluated on axial images of the fat map at the mid-level of T11-L2 vertebral bodies for BM fat and at the mid-level of L2 for PSM fat. Age, height, and weight at the time of MRI were recorded and BMI was calculated. Correlation analysis was performed. RESULTS A total of 147 patients (114 male) were included with a mean age of 13.3 ± 2.9 years (range 7-18 years). The mean fat fractions were 24.3 ± 13.0% (2-53%) in liver, 37.4 ± 8.6% (17.3-56%) in vertebral BM, and 2.7 ± 1.1% (1.0-6.9%) in PSM. Age, height, weight, and BMI were not correlated with liver fat or BM fat. However, weight (ρ = 0.174, p = 0.035) and BMI (ρ = 0.247, p = 0.003) were positively correlated with PSM fat. Liver fat showed positive correlation with BM fat when adjusting age and BMI (ρ = 0.309, p<0.001), but not with PSM fat. CONCLUSIONS BM fat positively correlates with liver fat, but not with age or BMI in pediatric NAFLD patients.
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Affiliation(s)
- Salman S. Albakheet
- Department of Radiology, Severance Hospital, Severance Pediatric Liver Disease Research Group, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, South Korea
- Department of Radiology, King Faisal General Hospital, Al-Hofuf, Kingdom of Saudi Arabia
| | - Haesung Yoon
- Department of Radiology, Severance Hospital, Severance Pediatric Liver Disease Research Group, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, South Korea
| | - Hyun Joo Shin
- Department of Radiology, Severance Hospital, Severance Pediatric Liver Disease Research Group, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, South Korea
| | - Hong Koh
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Severance Children’s Hospital, Severance Pediatric Liver Disease Research Group, Yonsei University College of Medicine, Seoul, South Korea
| | - Seung Kim
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Severance Children’s Hospital, Severance Pediatric Liver Disease Research Group, Yonsei University College of Medicine, Seoul, South Korea
| | - Mi-Jung Lee
- Department of Radiology, Severance Hospital, Severance Pediatric Liver Disease Research Group, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, South Korea
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Nabil M, El Demellawy MA, Mahmoud MF, Mahmoud AAA. Prolonged overnutrition with fructose or fat induces metabolic derangements in rats by disrupting the crosstalk between the hypothalamus and periphery: Possible amelioration with fenofibrate. Eur J Pharmacol 2020; 879:173136. [PMID: 32360834 DOI: 10.1016/j.ejphar.2020.173136] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 04/14/2020] [Accepted: 04/20/2020] [Indexed: 11/15/2022]
Abstract
Metabolic Syndrome (MetS) increases the risk of developing type 2 diabetes mellitus and cardiovascular complications. The crosstalk between the hypothalamus and periphery is vital for regulating food intake and energy homeostasis. However, it is impaired during MetS. The present study aimed to compare the distinct central and peripheral metabolic derangements induced by a high-fructose drink or high-fat diet, as well as the possible intervention by fenofibrate. Rats were divided into five groups: standard chow diet (SCD) group, high-fructose group (FR), high-fat group (HF), FR plus fenofibrate group (FR-F), and HF plus fenofibrate group (HF-F). FR and HF groups showed hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hyperleptinemia, steatosis, and adipocyte hypertrophy. This was associated with elevated circulating levels of proinflammatory cytokines and free fatty acids (FFAs). The latter mediators are involved in the hypothalamic inflammation and dysregulation of signaling cascades that control food intake and glucose homeostasis. The effects were more pronounced in the HF group than FR group, which were matched with the observed higher levels of plasma FFAs and cytokines. Fenofibrate administration improved not only the peripheral metabolic disturbances, but also the central disturbances associated with insulin resistance induced by FR or HF diet. This study sheds light on the pivotal role of the hypothalamus in diet-induced MetS. Furthermore, the study suggests the utmost importance of developing a standardized model of metabolic syndrome in place of the great diversity between available models, which can induce different effects and negatively impact the validity of prospective studies.
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Affiliation(s)
- Mohamed Nabil
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt; Pharmaceutical and Fermentation Industries Development Center (PFIDC), City of Scientific Research and Technological Applications (SRTA-City), New Borg El-Arab, Alexandria, 21934, Egypt
| | - Maha A El Demellawy
- Department of Medical Biotechnology, Genetic Engineering & Biotechnology Research Institute (GEBRI), City of Scientific Research and Technological Applications (SRTA-City), New Borg El-Arab, Alexandria, 21934, Egypt
| | - Mona F Mahmoud
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt
| | - Amr A A Mahmoud
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
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Vega-Martín E, González-Blázquez R, Manzano-Lista FJ, Martín-Ramos M, García-Prieto CF, Viana M, Rubio MA, Calle-Pascual AL, Lionetti L, Somoza B, Fernández-Alfonso MS, Alcalá M, Gil-Ortega M. Impact of caloric restriction on AMPK and endoplasmic reticulum stress in peripheral tissues and circulating peripheral blood mononuclear cells from Zucker rats. J Nutr Biochem 2020; 78:108342. [PMID: 32004927 DOI: 10.1016/j.jnutbio.2020.108342] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 12/27/2019] [Accepted: 01/03/2020] [Indexed: 12/17/2022]
Abstract
The activation of endoplasmic reticulum (ER) stress and a reduction of AMP-dependent protein kinase (AMPK) phosphorylation have been described in obesity. We hypothesize that a moderate caloric restriction (CR) might contribute to reducing ER stress and increasing AMPK phosphorylation in peripheral tissues from genetically obese Zucker fa/fa rats and in peripheral blood mononuclear cells (PBMCs). Zucker Lean and Zucker fa/fa rats were fed with chow diet either ad libitum (AL) (C, as controls) or 80% of AL (CR) for 2 weeks, giving rise to four experimental groups: Lean C, Lean CR, fa/fa C and fa/fa CR. CR significantly increased AMPK phosphorylation in the liver, perirenal adipose tissue (PRAT) and PBMCs from fa/fa rats but not in the subcutaneous AT (SCAT), suggesting a reduced response of SCAT to CR. Liver samples of fa/fa rats exhibited an increased mRNA expression of PERK, EIF-2α, XBP-1(s), Chop and caspase 3, which was significantly reduced by CR. PRAT exhibited an overexpression of Edem and PDIA-4 in fa/fa rats, but only PDIA-4 expression was reduced by CR. eIF-2α phosphorylation was significantly increased in all studied tissues from fa/fa rats and reduced by CR. A negative correlation was detected between p-AMPK and p-eIF-2α in the liver, PRAT and PBMCs from fa/fa rats but not in SCAT. This study shows that a moderate CR reduces ER stress and improves AMPK phosphorylation in several peripheral tissues and in circulating PBMCs, suggesting that alterations observed in PBMCs could reflect metabolic alterations associated with obesity.
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Affiliation(s)
- Elena Vega-Martín
- Instituto Pluridisciplinar, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain
| | - Raquel González-Blázquez
- Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, 28925, Madrid, Spain
| | - Francisco J Manzano-Lista
- Instituto Pluridisciplinar, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain
| | - Miriam Martín-Ramos
- Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, 28925, Madrid, Spain
| | - Concepción F García-Prieto
- Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, 28925, Madrid, Spain
| | - Marta Viana
- Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, 28925, Madrid, Spain
| | - Miguel A Rubio
- Department of Endocrinology and Nutrition, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Facultad de Medicina, Complutense University, C/ Prof. Martin Lagos s/n, 28040 Madrid, Spain
| | - Alfonso L Calle-Pascual
- Department of Endocrinology and Nutrition, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Facultad de Medicina, Complutense University, C/ Prof. Martin Lagos s/n, 28040 Madrid, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain
| | - Lillà Lionetti
- Department of Chemistry and Biology "A. Zambelli", University of Salerno, Via Giovanni Paolo II, 132, Fisciano, 84084, Italy
| | - Beatriz Somoza
- Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, 28925, Madrid, Spain
| | - María S Fernández-Alfonso
- Instituto Pluridisciplinar, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain
| | - Martín Alcalá
- Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, 28925, Madrid, Spain
| | - Marta Gil-Ortega
- Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, 28925, Madrid, Spain.
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Bourgeois C, Gorwood J, Barrail-Tran A, Lagathu C, Capeau J, Desjardins D, Le Grand R, Damouche A, Béréziat V, Lambotte O. Specific Biological Features of Adipose Tissue, and Their Impact on HIV Persistence. Front Microbiol 2019; 10:2837. [PMID: 31921023 PMCID: PMC6927940 DOI: 10.3389/fmicb.2019.02837] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Accepted: 11/22/2019] [Indexed: 12/19/2022] Open
Abstract
Although white AT can contribute to anti-infectious immune responses, it can also be targeted and perturbed by pathogens. The AT's immune involvement is primarily due to strong pro-inflammatory responses (with both local and paracrine effects), and the large number of fat-resident macrophages. Adipocytes also exert direct antimicrobial responses. In recent years, it has been found that memory T cells accumulate in AT, where they provide efficient secondary responses against viral pathogens. These observations have prompted researchers to re-evaluate the links between obesity and susceptibility to infections. In contrast, AT serves as a reservoir for several persistence pathogens, such as human adenovirus Ad-36, Trypanosoma gondii, Mycobacterium tuberculosis, influenza A virus, and cytomegalovirus (CMV). The presence and persistence of bacterial DNA in AT has led to the concept of a tissue-specific microbiota. The unexpected coexistence of immune cells and pathogens within the specific AT environment is intriguing, and its impact on anti-infectious immune responses requires further evaluation. AT has been recently identified as a site of HIV persistence. In the context of HIV infection, AT is targeted by both the virus and the antiretroviral drugs. AT's intrinsic metabolic features, large overall mass, and wide distribution make it a major tissue reservoir, and one that may contribute to the pathophysiology of chronic HIV infections. Here, we review the immune, metabolic, viral, and pharmacological aspects that contribute to HIV persistence in AT. We also evaluate the respective impacts of both intrinsic and HIV-induced factors on AT's involvement as a viral reservoir. Lastly, we examine the potential consequences of HIV persistence on the metabolic and immune activities of AT.
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Affiliation(s)
- Christine Bourgeois
- Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, CEA, Université Paris Sud, INSERM U1184, Fontenay-aux-Roses, France
| | - Jennifer Gorwood
- INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-Métabolisme et Nutrition (ICAN), Sorbonne Université, Paris, France
| | - Aurélie Barrail-Tran
- Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, CEA, Université Paris Sud, INSERM U1184, Fontenay-aux-Roses, France
- AP-HP, Service de Médecine Interne et Immunologie Clinique, Hôpital Bicêtre, Groupe Hospitalier Universitaire Paris Sud, Le Kremlin-Bicêtre, France
| | - Claire Lagathu
- INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-Métabolisme et Nutrition (ICAN), Sorbonne Université, Paris, France
| | - Jacqueline Capeau
- INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-Métabolisme et Nutrition (ICAN), Sorbonne Université, Paris, France
| | - Delphine Desjardins
- Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, CEA, Université Paris Sud, INSERM U1184, Fontenay-aux-Roses, France
| | - Roger Le Grand
- Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, CEA, Université Paris Sud, INSERM U1184, Fontenay-aux-Roses, France
| | - Abderaouf Damouche
- Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, CEA, Université Paris Sud, INSERM U1184, Fontenay-aux-Roses, France
| | - Véronique Béréziat
- INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-Métabolisme et Nutrition (ICAN), Sorbonne Université, Paris, France
| | - Olivier Lambotte
- Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, CEA, Université Paris Sud, INSERM U1184, Fontenay-aux-Roses, France
- AP-HP, Service de Médecine Interne et Immunologie Clinique, Hôpital Bicêtre, Groupe Hospitalier Universitaire Paris Sud, Le Kremlin-Bicêtre, France
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Covarrubias Y, Fowler KJ, Mamidipalli A, Hamilton G, Wolfson T, Leinhard OD, Jacobsen G, Horgan S, Schwimmer JB, Reeder SB, Sirlin CB. Pilot study on longitudinal change in pancreatic proton density fat fraction during a weight-loss surgery program in adults with obesity. J Magn Reson Imaging 2019; 50:1092-1102. [PMID: 30701611 PMCID: PMC6667307 DOI: 10.1002/jmri.26671] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Revised: 01/14/2019] [Accepted: 01/15/2019] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Quantitative-chemical-shift-encoded (CSE)-MRI methods have been applied to the liver. The feasibility and potential utility CSE-MRI in monitoring changes in pancreatic proton density fat fraction (PDFF) have not yet been demonstrated. PURPOSE To use quantitative CSE-MRI to estimate pancreatic fat changes during a weight-loss program in adults with severe obesity and nonalcoholic fatty liver disease (NAFLD). To explore the relationship of reduction in pancreatic PDFF with reductions in anthropometric indices. STUDY TYPE Prospective/longitudinal. POPULATION Nine adults with severe obesity and NAFLD enrolled in a weight-loss program. FIELD STRENGTH/SEQUENCE CSE-MRI fat quantification techniques and multistation-volumetric fat/water separation techniques were performed at 3 T. ASSESSMENT PDFF values were recorded from parametric maps colocalized across timepoints. STATISTICAL TESTS Rates of change of log-transformed variables across time were determined (linear-regression), and their significance assessed compared with no change (Wilcoxon test). Rates of change were correlated pairwise (Spearman's correlation). RESULTS Mean pancreatic PDFF decreased by 5.7% (range 0.7-17.7%) from 14.3 to 8.6%, hepatic PDFF by 11.4% (2.6-22.0%) from 14.8 to 3.4%, weight by 30.9 kg (17.3-64.2 kg) from 119.0 to 88.1 kg, body mass index by 11.0 kg/m2 (6.3-19.1 kg/m2 ) from 44.1 to 32.9 kg/m2 , waist circumference (WC) by 25.2 cm (4.0-41.0 cm) from 133.1 to 107.9 cm, HC by 23.5 cm (4.5-47.0 cm) from 135.8 to 112.3 cm, visceral adipose tissue (VAT) by 2.9 L (1.7-5.7 L) from 7.1 to 4.2 L, subcutaneous adipose tissue (SCAT) by 4.0 L (2.9-7.4 L) from 15.0 to 11.0 L. Log-transformed rate of change for pancreatic PDFF was moderately correlated with log-transformed rates for hepatic PDFF, VAT, SCAT, and WC (ρ = 0.5, 0.47, 0.45, and 0.48, respectively), although not statistically significant. DATA CONCLUSION Changes in pancreatic PDFF can be estimated by quantitative CSE-MRI in adults undergoing a weight-loss surgery program. Pancreatic and hepatic PDFF and anthropometric indices decreased significantly. LEVEL OF EVIDENCE 2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;50:1092-1102.
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Affiliation(s)
- Yesenia Covarrubias
- Liver Imaging Group, Department of Radiology, University of California, San Diego School of Medicine, La Jolla, California
| | - Kathryn J Fowler
- Liver Imaging Group, Department of Radiology, University of California, San Diego School of Medicine, La Jolla, California
| | - Adrija Mamidipalli
- Liver Imaging Group, Department of Radiology, University of California, San Diego School of Medicine, La Jolla, California
| | - Gavin Hamilton
- Liver Imaging Group, Department of Radiology, University of California, San Diego School of Medicine, La Jolla, California
| | - Tanya Wolfson
- Computational and Applied Statistics Laboratory, San Diego Supercomputer Center, University of California, San Diego, La Jolla, California
| | - Olof Dahlqvist Leinhard
- AMRA Medical AB, Linköping, Sweden
- Center for Medical Image Science and Visualization, Linköping, Sweden
- Department of Medicine and Health, Linköping, University, Linköping, Sweden
| | - Garth Jacobsen
- Department of Surgery, University of California, San Diego, La Jolla, California
| | - Santiago Horgan
- Department of Surgery, University of California, San Diego, La Jolla, California
| | - Jeffrey B Schwimmer
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego, La Jolla, California
- Department of Gastroenterology, Rady Children’s Hospital San Diego, San Diego, California
| | - Scott B Reeder
- Department of Radiology, University of Wisconsin - Madison, Madison, Wisconsin
- Department of Medical Physics, University of Wisconsin - Madison, Madison, Wisconsin
- Department of Biomedical Engineering, University of Wisconsin - Madison, Madison, Wisconsin
- Department of Medicine, University of Wisconsin - Madison, Madison, Wisconsin
| | - Claude B Sirlin
- Liver Imaging Group, Department of Radiology, University of California, San Diego School of Medicine, La Jolla, California
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Abstract
Nutrient overload occurs worldwide as a consequence of the modern diet pattern and the physical inactivity that sometimes accompanies it. Cells initiate multiple protective mechanisms to adapt to elevated intracellular metabolites and restore metabolic homeostasis, but irreversible injury to the cells can occur in the event of prolonged nutrient overload. Many studies have advanced the understanding of the different detrimental effects of nutrient overload; however, few reports have made connections and given the full picture of the impact of nutrient overload on cellular metabolism. In this review, detailed changes in metabolic and energy homeostasis caused by chronic nutrient overload, as well as their associations with the development of metabolic disorders, are discussed. Overnutrition-induced changes in key organelles and sensors rewire cellular bioenergetic pathways and facilitate the shift of the metabolic state toward biosynthesis, thereby leading to the onset of various metabolic disorders, which are essentially the downstream manifestations of a misbalanced metabolic equilibrium. Based on these mechanisms, potential therapeutic targets for metabolic disorders and new research directions are proposed.
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Affiliation(s)
- Haowen Qiu
- Department of Nutrition and Health Sciences and Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, Nebraska, USA
| | - Vicki Schlegel
- Department of Nutrition and Health Sciences and Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, Nebraska, USA
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50
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Migliaccio V, Gregorio ID, Putti R, Lionetti L. Mitochondrial Involvement in the Adaptive Response to Chronic Exposure to Environmental Pollutants and High-Fat Feeding in a Rat Liver and Testis. Cells 2019; 8:E834. [PMID: 31387296 PMCID: PMC6721750 DOI: 10.3390/cells8080834] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 07/28/2019] [Accepted: 08/03/2019] [Indexed: 02/07/2023] Open
Abstract
In our modern society, exposure to stressful environmental stimuli, such as pollutants and/or chronic high-fat feeding, continuously induce tissular/organ metabolic adaptation to promote cellular survival. In extreme conditions, cellular death and tissular/organ damage occur. Mitochondria, as a cellular energy source, seem to play an important role in facing cellular stress induced by these environmental stimuli. On the other hand, mitochondrial dysfunction and oxidative stress play a key role in environmental stress-induced metabolic diseases. However, little is known about the combined effect of simultaneous exposure to chronic high-fat feeding and environmental pollutants on metabolic alterations at a tissular and cellular level, including mitochondrial dysfunction and oxidative stress induction. Our research group recently addressed this topic by analysing the effect of chronic exposure to a non-toxic dose of the environmental pollutant dichlorodiphenyldichloroethylene (DDE) associated with high-fat feeding in male Wistar rats. In this review, we mainly summarize our recent findings on mitochondrial adaptive response and oxidative stress induction in the liver, the main tissue involved in fat metabolism and pollutant detoxification, and in male gonads, the main targets of endocrine disruption induced by both high-fat feeding and environmental pollutants.
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Affiliation(s)
- Vincenzo Migliaccio
- Department of Chemistry and Biology "Adolfo Zambelli", University of Salerno, 84084 Fisciano, Italy.
- Department of Biology, University of Naples, Federico II, 80126 Naples, Italy.
| | - Ilaria Di Gregorio
- Department of Chemistry and Biology "Adolfo Zambelli", University of Salerno, 84084 Fisciano, Italy
| | - Rosalba Putti
- Department of Biology, University of Naples, Federico II, 80126 Naples, Italy
| | - Lillà Lionetti
- Department of Chemistry and Biology "Adolfo Zambelli", University of Salerno, 84084 Fisciano, Italy.
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