|
1
|
Ghosh A, Chénier I, Leung YH, Oppong AK, Peyot ML, Madiraju SRM, Al-Khairi I, Abubaker J, Al-Mulla F, Prentki M, Abu-Farha M. Adipocyte Angptl8 deletion improves glucose and energy metabolism and obesity associated inflammation in mice. iScience 2024; 27:111292. [PMID: 39640567 PMCID: PMC11617963 DOI: 10.1016/j.isci.2024.111292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 08/28/2024] [Accepted: 10/28/2024] [Indexed: 12/07/2024] Open
Abstract
Angiopoietin-like protein 8 (Angptl8), expressed in the liver and adipocytes, forms a complex with Angptl3 or Angptl4, which regulates lipoprotein lipase and triglyceride metabolism. However, the precise functions of adipocyte Angptl8 remain elusive. Here we report that adipocyte-specific inducible Angptl8-knockout (AT-A8-KO) male mice on normal diet showed minor phenotypic changes, but after a high-fat high fructose (HFHF) diet, exhibited decreased body weight gain and glycemia, elevated rectal temperature and early dark phase energy expenditure compared to the Cre controls. AT-A8-KO mice also displayed improved glucose tolerance, a trend for better insulin sensitivity, improved insulin-stimulated glucose uptake in adipose tissues, and reduced visceral adipose tissue crown-like structures, plasma MCP-1 and leptin levels. The results indicate the importance of adipose Angptl8 in the context of nutri-stress and obesity, as its deletion in mice promotes a metabolically healthy obese phenotype by slightly ameliorating obesity, improving glucose and energy homeostasis, and mitigating inflammation.
Collapse
Affiliation(s)
- Anindya Ghosh
- Departments of Nutrition, Biochemistry and Molecular Medicine, University of Montreal, and Montreal Diabetes Research Center, Centre de Recherche Du Centre Hospitalier de L’Université de Montréal (CRCHUM), Montréal, QC, Canada
| | - Isabelle Chénier
- Departments of Nutrition, Biochemistry and Molecular Medicine, University of Montreal, and Montreal Diabetes Research Center, Centre de Recherche Du Centre Hospitalier de L’Université de Montréal (CRCHUM), Montréal, QC, Canada
| | - Yat Hei Leung
- Departments of Nutrition, Biochemistry and Molecular Medicine, University of Montreal, and Montreal Diabetes Research Center, Centre de Recherche Du Centre Hospitalier de L’Université de Montréal (CRCHUM), Montréal, QC, Canada
| | - Abel K. Oppong
- Departments of Nutrition, Biochemistry and Molecular Medicine, University of Montreal, and Montreal Diabetes Research Center, Centre de Recherche Du Centre Hospitalier de L’Université de Montréal (CRCHUM), Montréal, QC, Canada
| | - Marie-Line Peyot
- Departments of Nutrition, Biochemistry and Molecular Medicine, University of Montreal, and Montreal Diabetes Research Center, Centre de Recherche Du Centre Hospitalier de L’Université de Montréal (CRCHUM), Montréal, QC, Canada
| | - S. R. Murthy Madiraju
- Departments of Nutrition, Biochemistry and Molecular Medicine, University of Montreal, and Montreal Diabetes Research Center, Centre de Recherche Du Centre Hospitalier de L’Université de Montréal (CRCHUM), Montréal, QC, Canada
| | - Irina Al-Khairi
- Biochemistry and Molecular Biology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait
| | - Jehad Abubaker
- Biochemistry and Molecular Biology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait
| | - Fahd Al-Mulla
- Translational Research Department, Dasman Diabetes Institute, Dasman 15462, Kuwait
| | - Marc Prentki
- Departments of Nutrition, Biochemistry and Molecular Medicine, University of Montreal, and Montreal Diabetes Research Center, Centre de Recherche Du Centre Hospitalier de L’Université de Montréal (CRCHUM), Montréal, QC, Canada
| | - Mohamed Abu-Farha
- Biochemistry and Molecular Biology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait
- Translational Research Department, Dasman Diabetes Institute, Dasman 15462, Kuwait
| |
Collapse
|
|
2
|
Masemola M, Mendham AE, Micklesfield LK, Pheiffer C, Hawley J, Kengne AP, Chikowore T, Kufe CN, Crowther NJ, Norris S, Storbeck KH, Olsson T, Karpe F, Goedecke JH. Regional Adiposity and Insulin Sensitivity-Interactions With Menopause and HIV in Middle-Aged Black African Women. J Clin Endocrinol Metab 2024; 110:16-29. [PMID: 38950129 DOI: 10.1210/clinem/dgae447] [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: 03/14/2024] [Revised: 06/27/2024] [Accepted: 06/27/2024] [Indexed: 07/03/2024]
Abstract
OBJECTIVE To explore depot-specific functional aspects of adipose tissue, examining the putative role for menopause and HIV status on insulin sensitivity (SI) and beta-cell function in Black South African women. METHODS Women (n = 92) from the Middle-Aged Soweto Cohort, including premenopausal HIV-negative women (n = 21); premenopausal women living with HIV (LWH; n = 11); postmenopausal HIV-negative women (n = 42); and postmenopausal women LWH (n = 18) underwent the following tests: body composition (dual-energy x-ray absorptiometry); fasting bloods for sex hormones, inflammation, and adipokines; frequently sampled intravenous glucose tolerance test for SI and beta-cell function (disposition index, DI); abdominal (aSAT) and gluteal subcutaneous adipose tissue (gSAT) biopsies for cell size, and mRNA expression of adipokines, inflammation, and estrogen receptors (ER). RESULTS Depot-specific associations between gene expression and insulin parameters did not differ by HIV or menopause status. Pooled analysis showed significant models for SI (P = .002) and DI (P = .003). Higher SI was associated with lower leptin and CD11c expression in aSAT and higher adiponectin in gSAT. Higher DI was associated with higher aSAT and gSAT expression of adiponectin, lipoprotein lipase, ERα, and PPARγ, and lower leptin in aSAT. Women LWH had higher expression of adiponectin and lower expression of leptin in both aSAT (P = .002 and P = .005) and gSAT (P = .004 and P = .002), respectively, and a larger proportion of smaller cells in aSAT (P < .001). CONCLUSION Insulin sensitivity and beta-cell function were distinctively associated with aSAT and gSAT. While menopause did not influence these relationships, HIV had a significant effect on adipose tissue, characterized by variations in cell size distribution and transcript levels within the depots.
Collapse
Affiliation(s)
- Maphoko Masemola
- South African Medical Research Council/WITS Developmental Pathways for Health Research Unit (DPHRU), Department of Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa
| | - Amy E Mendham
- South African Medical Research Council/WITS Developmental Pathways for Health Research Unit (DPHRU), Department of Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa
- Riverland Academy of Clinical Excellence, Riverland Mallee Coorong Local Health Network, South Australia Health, Berri, 5343, South Australia, Australia
- Health through Physical Activity, Lifestyle and Sport Research Centre (HPALS), FIMS International Collaborating Centre of Sports Medicine, Division of Physiological Sciences, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, 7700, South Africa
| | - Lisa K Micklesfield
- South African Medical Research Council/WITS Developmental Pathways for Health Research Unit (DPHRU), Department of Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa
| | - Carmen Pheiffer
- Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, Cape Town, 7505, South Africa
- Centre for Cardiometabolic Research in Africa (CARMA), Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, 7505, South Africa
- Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of Pretoria, Pretoria, 0002, South Africa
| | - James Hawley
- Department of Biochemistry, Manchester University, NHS foundation Trust, Manchester, M13 9WL, UK
| | - Andre Pascal Kengne
- Non-Communicable Diseases Research Unit, South African Medical Research Council, Tygerberg, Cape Town, 7505, South Africa
| | - Tinashe Chikowore
- South African Medical Research Council/WITS Developmental Pathways for Health Research Unit (DPHRU), Department of Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa
| | - Clement Nyuyki Kufe
- South African Medical Research Council/WITS Developmental Pathways for Health Research Unit (DPHRU), Department of Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa
- Department of Anaesthesiology, School of Clinical Medicine, University of the Witwatersrand, Faculty of Health Sciences, Johannesburg, 2050, South Africa
| | - Nigel J Crowther
- Department of Chemical Pathology, National Health Laboratory Service and University of the Witwatersrand, Faculty of Health Sciences, Johannesburg, 2192, South Africa
| | - Shane Norris
- South African Medical Research Council/WITS Developmental Pathways for Health Research Unit (DPHRU), Department of Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa
| | - Karl-Heinz Storbeck
- Department of Biochemistry, Stellenbosch University, Stellenbosch, 7600, South Africa
| | - Tommy Olsson
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, 901 87, Sweden
| | - Fredrik Karpe
- Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, OX3 7LE, UK
- National Institute for Health Research, Oxford Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, OX3 7LE, UK
| | - Julia H Goedecke
- South African Medical Research Council/WITS Developmental Pathways for Health Research Unit (DPHRU), Department of Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa
- Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, Cape Town, 7505, South Africa
| |
Collapse
|
|
3
|
Zaidalkilani AT, Al‐Kuraishy HM, Al‐Gareeb AI, Alexiou A, Papadakis M, AL‐Farga A, Alghamdi OA, Bahaa MM, Alrouji M, Alshammari MS, Batiha GE. The beneficial and detrimental effects of prolactin hormone on metabolic syndrome: A double-edge sword. J Cell Mol Med 2024; 28:e70067. [PMID: 39663784 PMCID: PMC11635126 DOI: 10.1111/jcmm.70067] [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: 09/14/2023] [Revised: 08/19/2024] [Accepted: 08/24/2024] [Indexed: 12/13/2024] Open
Abstract
The metabolic syndrome (MetS) is a clustering of abdominal obesity, hypertension, hyperglycaemia, hypertriglyceridemia and low high-density lipoprotein (HDL) level. MetS development is affected by endocrine hormones such as prolactin (PRL) hormone which induce insulin resistance and central obesity because PRL is implicated in the pathogenesis of MetS. Pituitary PRL controls mammary gland, however extra-pituitary PRL is highly intricate in the regulation of adipose tissue function. In addition, cAMP activators enhance expression and release of PRL which involved in the control of lipogenesis and energy homeostasis. Consequently, hyperprolactinaemia may be associated with the development of MetS. However, normal physiological level of PRL is essential for insulin sensitivity and regulation of adipose tissue function and energy metabolism. Therefore, PRL has dual effects on the components of MetS. Hence, the present review aims to discuss the modulatory mechanistic role of PRL on MetS regarding its beneficial and detrimental effects.
Collapse
Affiliation(s)
- Ayah Talal Zaidalkilani
- Department of Nutrition, Faculty of Pharmacy and Medical SciencesUniversity of PetraAmman11196Jordan
| | - Hayder M. Al‐Kuraishy
- Department of Clinical pharmacology and MedicineCollege of Medicine, Mustansiriyah UniversityBaghdadIraq
| | - Ali I. Al‐Gareeb
- Department of Clinical pharmacology and MedicineCollege of Medicine, Mustansiriyah UniversityBaghdadIraq
| | - Athanasios Alexiou
- Department of Science and EngineeringNovel Global Community Educational FoundationHebershamNew South WalesAustralia
- AFNP MedWienAustria
- University Centre for Research & DevelopmentChandigarh UniversityMohaliPunjabIndia
- Department of Research & DevelopmentFunogenAthensGreece
| | - Marios Papadakis
- Department of Surgery IIUniversity Hospital Witten‐Herdecke, Heusnerstrasse 40, University of Witten‐HerdeckeWuppertalGermany
| | - Ammar AL‐Farga
- Department of BiochemistryCollege of Science University of JeddahJeddahSaudi Arabia
| | - Othman A. Alghamdi
- Department of Biological SciencesCollege of Science, University of JeddahJeddahSaudi Arabia
| | - Mostafa M. Bahaa
- Pharmacy Practice Department, Faculty of PharmacyHorus UniversityNew DamiettaEgypt
| | - Mohammed Alrouji
- Department of Clinical Laboratory SciencesCollege of Applied Medical Sciences, Shaqra UniversityShaqraSaudi Arabia
| | - Mohammed S. Alshammari
- Department of Clinical Laboratory SciencesCollege of Applied Medical Sciences, Shaqra UniversityShaqraSaudi Arabia
| | - Gaber El‐Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary MedicineDamanhour UniversityDamanhourEgypt
| |
Collapse
|
|
4
|
Łukaszuk B, Supruniuk E, Chabowski A, Mikłosz A. Altered Cytokine Secretory Fingerprint of the Adipocytes Derived from Stem Cells of Morbidly Obese Patients-A Preliminary Study. Cells 2024; 13:1603. [PMID: 39404367 PMCID: PMC11475718 DOI: 10.3390/cells13191603] [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] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 09/18/2024] [Accepted: 09/23/2024] [Indexed: 10/19/2024] Open
Abstract
Context: Adipose-derived mesenchymal stem cells (ADMSCs) are progenitor cells that shape the tissue's biological properties. Objective: To examine the adipocytes differentiated from the ADMSCs of lean and obese individuals with/without a metabolic syndrome (MetSx) cytokine secretory profile, as to date, little is known on this topic. Methods: Interleukin, chemokine and growth factor levels in the culture medium were determined using the Human Cytokine kit. Results: We observed a characteristic secretory fingerprint displayed by the cells from the MetSx group and identified a set of putative markers (IL-1β, IL-6, IL-7, IL-10, IL-12, IL-13, VEGF, FGF, GM-CSF, TNF-α, IFN-γ) of the condition. Surprisingly, the concentrations of most of the molecules (except for IL-6, IFN-γ, IP-10, VEGF) decreased when compared with the cells from the lean group. We postulate that the difference stemmed from the fact that in vivo cytokines were mostly secreted by the activated monocytes/macrophages and not adipocytes per se. This may also suggest that the aforementioned upregulated cytokines (IL-6, IFN-γ, IP-10, VEGF) might have been the ones that attracted monocytes and triggered the vicious cycle of tissue inflammation. Conclusions: Our study indicated that the adipocytes newly derived from the ADMSCs of obese patients with metabolic syndrome displayed a secretory fingerprint that may be characteristic to the early stages of the condition.
Collapse
Affiliation(s)
- Bartłomiej Łukaszuk
- Department of Physiology, Medical University of Bialystok, 15-089 Bialystok, Poland; (E.S.); (A.M.)
| | | | | | | |
Collapse
|
|
5
|
Randeni N, Bordiga M, Xu B. A Comprehensive Review of the Triangular Relationship among Diet-Gut Microbiota-Inflammation. Int J Mol Sci 2024; 25:9366. [PMID: 39273314 PMCID: PMC11394685 DOI: 10.3390/ijms25179366] [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: 07/17/2024] [Revised: 08/21/2024] [Accepted: 08/27/2024] [Indexed: 09/15/2024] Open
Abstract
The human gastrointestinal tract hosts a complex and dynamic community of microorganisms known as the gut microbiota, which play a pivotal role in numerous physiological processes, including digestion, metabolism, and immune function. Recent research has highlighted the significant impact of diet on the gut microbiota composition and functionality, and the consequential effects on host health. Concurrently, there is growing evidence linking the gut microbiota to inflammation, a key factor in many chronic diseases such as inflammatory bowel disease (IBD), obesity, diabetes, and cardiovascular diseases (CVDs). This review explores how dietary components influence the gut microbiota composition, how these microbial changes affect inflammatory pathways, and the therapeutic implications of modulating this axis for chronic inflammatory disease prevention and management. Beneficial dietary patterns, such as the Mediterranean diet (MD) and plant-based diets, promote a diverse and balanced gut microbiota composition, supporting anti-inflammatory pathways. Conversely, the Western diet (WD), high in saturated fats and refined sugars, is associated with dysbiosis and increased inflammation. With all the links between the three variables considered, this review attempts to offer a thorough examination of the triangle formed by inflammation, the gut microbiota, and food.
Collapse
Affiliation(s)
- Nidesha Randeni
- Food Science and Technology Program, Department of Life Sciences, BNU-HKBU United International College, Zhuhai 519087, China
- Department of Agricultural and Plantation Engineering, Faculty of Engineering Technology, The Open University of Sri Lanka, Nawala, Nugegoda 10250, Sri Lanka
| | - Matteo Bordiga
- Department of Pharmaceutical Sciences, Università degli Studi del Piemonte Orientale "A. Avogadro", Largo Donegani 2, 28100 Novara, Italy
| | - Baojun Xu
- Food Science and Technology Program, Department of Life Sciences, BNU-HKBU United International College, Zhuhai 519087, China
| |
Collapse
|
|
6
|
Apaza CJ, Cerezo JF, García-Tejedor A, Giménez-Bastida JA, Laparra-Llopis JM. Revisiting the Immunometabolic Basis for the Metabolic Syndrome from an Immunonutritional View. Biomedicines 2024; 12:1825. [PMID: 39200288 PMCID: PMC11352112 DOI: 10.3390/biomedicines12081825] [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: 06/02/2024] [Revised: 07/11/2024] [Accepted: 08/06/2024] [Indexed: 09/02/2024] Open
Abstract
Metabolic syndrome (MetS) implies different conditions where insulin resistance constitutes a major hallmark of the disease. The disease incurs a high risk for the development of cardiovascular complications, and takes its toll in regard to the gut-liver axis (pancreas, primary liver and colorectal)-associated immunity. The modulation of immunometabolic responses by immunonutritional factors (IFs) has emerged as a key determinant of the gut-liver axis' metabolic and immune health. IFs from plant seeds have shown in vitro and pre-clinical effectiveness primarily in dealing with various immunometabolic and inflammatory diseases. Only recently have immunonutritional studies established the engagement of innate intestinal immunity to effectively control immune alterations in inflamed livers preceding the major features of the MetS. However, integrative analyses and the demonstration of causality between IFs and specific gut-liver axis-associated immunometabolic imbalances for the MetS remain ill-defined in the field. Herein, a better understanding of the IFs with a significant role in the MetS, as well as within the dynamic interplay in the functional differentiation of innate immune key effectors (i.e., monocytes/macrophages), worsening or improving the disease, could be of crucial relevance. The development of an adequate intermediary phenotype of these cells can significantly contribute to maintaining the function of Tregs and innate lymphoid cells for the prevention and treatment of MetS and associated comorbidities.
Collapse
Affiliation(s)
- César Jeri Apaza
- Madrid Institute for Advanced Studies in Food (IMDEA Food), Carretera Cantoblanco 8, 28049 Madrid, Spain
- Bioactivity and Nutritional Immunology Group (BIOINUT), Valencian International University (VIU), Pintor Sorolla 21, 46002 Valencia, Spain
| | - Juan Francisco Cerezo
- Madrid Institute for Advanced Studies in Food (IMDEA Food), Carretera Cantoblanco 8, 28049 Madrid, Spain
| | - Aurora García-Tejedor
- Bioactivity and Nutritional Immunology Group (BIOINUT), Valencian International University (VIU), Pintor Sorolla 21, 46002 Valencia, Spain
| | - Juan Antonio Giménez-Bastida
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Campus de Espinardo, CEBAS-CSIC, P.O. Box 164, 30100 Murcia, Spain;
| | - José Moisés Laparra-Llopis
- Madrid Institute for Advanced Studies in Food (IMDEA Food), Carretera Cantoblanco 8, 28049 Madrid, Spain
- Bioactivity and Nutritional Immunology Group (BIOINUT), Valencian International University (VIU), Pintor Sorolla 21, 46002 Valencia, Spain
| |
Collapse
|
|
7
|
Zhang G, Wang S, Ma P, Li S, Sun X, Zhao Y, Pan J. Increased regional body fat is associated with depressive symptoms: a cross-sectional analysis of NHANES data obtained during 2011-2018. BMC Psychiatry 2024; 24:336. [PMID: 38702637 PMCID: PMC11067210 DOI: 10.1186/s12888-024-05782-4] [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: 10/04/2023] [Accepted: 04/22/2024] [Indexed: 05/06/2024] Open
Abstract
AIMS The findings from previous epidemiological studies of the association between regional body fat and depressive symptoms have been unclear. We aimed to determine the association between the body fat in different regions and depressive symptoms based on data from the National Health and Nutrition Examination Survey (NHANES). METHODS This study included 3393 participants aged ≥ 20 years from the NHANES performed during 2011-2018. Depressive symptoms were assessed using the Patient Health Questionnaire-9. The fat mass (FM) was measured in different regions using dual-energy X-ray absorptiometry to determine the total FM, trunk FM, arm FM, and leg FM. The FM index (FMI) was obtained by dividing the FM in kilograms by the square of the body height in meters. Weighted data were calculated in accordance with analytical guidelines. Linear logistic regression models were used to quantify the association between regional FMI and depressive symptoms. Univariate and stratified analyses were also performed. RESULTS The participants in this study comprised 2066 males and 1327 females. There were 404 (11.91%) participants with depressive symptoms, who were aged 40.89 ± 11.74 years and had a body mass index of 30.07 ± 7.82 kg/m². A significant association was found between total FMI and depressive symptoms. In the fully adjusted multivariate regression model, a higher total FMI (odds ratio = 2.18, 95% confidence interval [CI] = 1.08-4.39) was related to a higher risk of depressive symptoms, while increased total FMI (β = 1.55, 95% CI = 0.65-2.44, p = 0.001), trunk FMI (β = 0.57, 95% CI = 0.04-1.10, p = 0.036), and arm FMI (β = 0.96, 95% CI = 0.33-1.59, p = 0.004) were significantly associated with PHQ-9 (Patient Health Questionnaire-9) scores, whereas the leg FMI was not (p = 0.102). The weighted association between total FMI and depressive symptoms did not differ significantly between most of the subpopulations (all p values for interaction > 0.05). The risk of having depression was higher in individuals who were non-Hispanic Whites, smokers, drinkers, obese, and had diabetes and thyroid problems (p < 0.05). CONCLUSION These findings suggest that the population with a higher regional FMI is more likely to have depressive symptoms, especially in those who also have an increased total FMI. The association is more pronounced in individuals who are smokers, drinkers, obese, and have diabetes and thyroid problems.
Collapse
Affiliation(s)
- GuiMei Zhang
- Department of Psychiatry, Sleep Medicine Centre, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, 510632, P.R. China
| | - Sisi Wang
- Department of Psychiatry, Sleep Medicine Centre, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, 510632, P.R. China
| | - Ping Ma
- Department of Psychiatry, Sleep Medicine Centre, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, 510632, P.R. China
| | - Shuna Li
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510632, China
| | - Xizhe Sun
- Department of Psychiatry, Sleep Medicine Centre, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, 510632, P.R. China
| | - Yang Zhao
- Department of Psychiatry, Sleep Medicine Centre, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, 510632, P.R. China
| | - Jiyang Pan
- Department of Psychiatry, Sleep Medicine Centre, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, 510632, P.R. China.
| |
Collapse
|
|
8
|
Sikder S, Pierce D, Sarkar ER, McHugh C, Quinlan KGR, Giacomin P, Loukas A. Regulation of host metabolic health by parasitic helminths. Trends Parasitol 2024; 40:386-400. [PMID: 38609741 DOI: 10.1016/j.pt.2024.03.006] [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: 02/12/2024] [Revised: 03/14/2024] [Accepted: 03/14/2024] [Indexed: 04/14/2024]
Abstract
Obesity is a worldwide pandemic and major risk factor for the development of metabolic syndrome (MetS) and type 2 diabetes (T2D). T2D requires lifelong medical support to limit complications and is defined by impaired glucose tolerance, insulin resistance (IR), and chronic low-level systemic inflammation initiating from adipose tissue. The current preventative strategies include a healthy diet, controlled physical activity, and medication targeting hyperglycemia, with underexplored underlying inflammation. Studies suggest a protective role for helminth infection in the prevention of T2D. The mechanisms may involve induction of modified type 2 and regulatory immune responses that suppress inflammation and promote insulin sensitivity. In this review, the roles of helminths in counteracting MetS, and prospects for harnessing these protective mechanisms for the development of novel anti-diabetes drugs are discussed.
Collapse
Affiliation(s)
- Suchandan Sikder
- Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland 4878, Australia.
| | - Doris Pierce
- Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland 4878, Australia
| | - Eti R Sarkar
- Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland 4878, Australia; College of Public Health, Medical and Veterinary Sciences, James Cook University, Cairns, Queensland 4878, Australia
| | - Connor McHugh
- Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland 4878, Australia; College of Public Health, Medical and Veterinary Sciences, James Cook University, Cairns, Queensland 4878, Australia
| | - Kate G R Quinlan
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, 2052, Australia
| | - Paul Giacomin
- Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland 4878, Australia; Macrobiome Therapeutics Pty Ltd, Cairns, Queensland 4878, Australia
| | - Alex Loukas
- Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland 4878, Australia; Macrobiome Therapeutics Pty Ltd, Cairns, Queensland 4878, Australia
| |
Collapse
|
|
9
|
Singh M, Kulshrestha R, Singh V, Pathak AK, Kumar A, Singh S, Bohra GK. Effects of Low and High Doses of Aspirin on Inflammatory Markers in Diabesity Patients: A Quasi-Experimental Study. Cureus 2024; 16:e60659. [PMID: 38899239 PMCID: PMC11186204 DOI: 10.7759/cureus.60659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/17/2024] [Indexed: 06/21/2024] Open
Abstract
Introduction The intertwined nature of obesity and diabetes, termed diabesity, is a significant health concern. Aspirin has been recognized for its potential in mitigating inflammation-related health issues, a key concern in managing diabesity. However, the optimal aspirin dosage and its impact on specific inflammatory markers, viz. high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6, over time remain a subject of ongoing research. Objective This study investigated the effects of different doses of aspirin (150mg and 300mg) on the levels of hs-CRP and IL-6 over a period of 6 months. Methods This cross-sectional observational quasi-experiment study involved 125 confirmed type-2 diabetes mellitus (T2DM) patients with obesity aged ≥40 years. Blood samples were collected for analyzing hs-CRP and IL-6 levels. Demographics and clinical characteristics, such as BMI, waist-hip ratio, blood parameters, fasting blood sugar (FBS), and hs-CRP, were analyzed. Results At baseline, both the 150 mg and 300 mg aspirin dose groups had similar median levels of hs-CRP. After two months, there was no significant difference (p=0.150). However, by six months, the 150mg dose group had a significantly higher median hs-CRP than the 300 mg dose group (p=0.003). The 150 mg dose group had a significantly higher median level of IL-6 levels at baseline (median; 40.0) compared to the 300 mg dose group (median; 2.27, p<0.0001). After two months, the levels of IL-6 in both groups were similar (median; 2.27 and 2.23 respectively, p<0.0001). By the end of six months, the groups had no significant difference (median; 0.53 and 2.22 respectively, p=0.128). Conclusion The dose of aspirin may significantly impact the levels of hs-CRP and IL-6 over time, with the effects being more pronounced after six months of treatment. These findings suggest that aspirin, a commonly used and cost-effective medication, could potentially be leveraged in a more targeted manner to manage inflammation (CRP and IL-6 levels) in individuals with diabesity.
Collapse
Affiliation(s)
- Mridu Singh
- Medicine, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, IND
| | - Rupita Kulshrestha
- Obstetrics and Gynaecology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, IND
| | - Vikram Singh
- Medicine, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, IND
| | - Anumesh K Pathak
- Biochemistry, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, IND
| | - Abhisek Kumar
- Medicine, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, IND
| | - Shivani Singh
- Biochemistry, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, IND
| | - Gopal K Bohra
- Medicine, All India Institute of Medical Sciences, Jodhpur, IND
| |
Collapse
|
|
10
|
Wu Y, Li Y, Sun M, Yu F, Liu H, Xu J, Tang X. FAP deficiency enhances thermogenesis and attenuates metabolic inflammation in diet-induced obesity. Obesity (Silver Spring) 2024; 32:528-539. [PMID: 38100123 DOI: 10.1002/oby.23955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Revised: 10/21/2023] [Accepted: 10/23/2023] [Indexed: 02/28/2024]
Abstract
OBJECTIVE Fibroblast activation protein α (FAP) is expressed in normal adipose tissue and related to some pleiotropic metabolic regulators. However, the exact role and mechanism of FAP in obesity and related metabolic disorders are not well understood. METHODS FAP knockout mice were fed a normal diet or a high-fat diet (HFD) for 12 weeks. FAP knockout mice or wild-type mice treated with an FAP inhibitor were subjected to cold stress for 5 days. RESULTS FAP deficiency protected mice against HFD-induced obesity and obesity-associated metabolic dysfunction, including glucose intolerance, insulin resistance, hyperglycemia, hyperinsulinemia, and hyperlipidemia. Notably, FAP deficiency largely reversed obesity-induced adipose tissue macrophage accumulation and M1-M2 imbalance in white adipose tissue (WAT). Moreover, energy expenditure was significantly higher in FAP-deficient mice fed an HFD. Both FAP deficiency and inhibition increased cold tolerance through enhancing WAT beiging. CONCLUSIONS This study demonstrated that FAP deficiency protects mice against diet-induced obesity and related metabolic dysfunction. Furthermore, the protective effects are probably mediated via the promotion of WAT beiging and suppression of inflammation.
Collapse
Affiliation(s)
- Yunyun Wu
- Department of Medical Microbiology and Immunology, Wannan Medical College, Wuhu, China
| | - Yun Li
- Department of Pharmacy, Wannan Medical College, Wuhu, China
| | - Miao Sun
- Department of Pharmacy, Wannan Medical College, Wuhu, China
| | - Fangliu Yu
- Department of Medical Microbiology and Immunology, Wannan Medical College, Wuhu, China
| | - Hui Liu
- Department of Medical Microbiology and Immunology, Wannan Medical College, Wuhu, China
| | - Jingyun Xu
- Department of Parasitology, Wannan Medical College, Wuhu, China
| | - Xingli Tang
- Department of Medical Microbiology and Immunology, Wannan Medical College, Wuhu, China
| |
Collapse
|
|
11
|
Tarabeih N, Kalinkovich A, Ashkenazi S, Cherny SS, Shalata A, Livshits G. Relationships between Circulating Biomarkers and Body Composition Parameters in Patients with Metabolic Syndrome: A Community-Based Study. Int J Mol Sci 2024; 25:881. [PMID: 38255954 PMCID: PMC10815336 DOI: 10.3390/ijms25020881] [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: 12/06/2023] [Revised: 01/07/2024] [Accepted: 01/08/2024] [Indexed: 01/24/2024] Open
Abstract
Metabolic syndrome (MetS) is a complex disease involving multiple physiological, biochemical, and metabolic abnormalities. The search for reliable biomarkers may help to better elucidate its pathogenesis and develop new preventive and therapeutic strategies. In the present population-based study, we looked for biomarkers of MetS among obesity- and inflammation-related circulating factors and body composition parameters in 1079 individuals (with age range between 18 and 80) belonging to an ethnically homogeneous population. Plasma levels of soluble markers were measured by using ELISA. Body composition parameters were assessed using bioimpedance analysis (BIA). Statistical analysis, including mixed-effects regression, with MetS as a dependent variable, revealed that the most significant independent variables were mainly adipose tissue-related phenotypes, including fat mass/weight (FM/WT) [OR (95% CI)], 2.77 (2.01-3.81); leptin/adiponectin ratio (L/A ratio), 1.50 (1.23-1.83); growth and differentiation factor 15 (GDF-15) levels, 1.32 (1.08-1.62); inflammatory markers, specifically monocyte to high-density lipoprotein cholesterol ratio (MHR), 2.53 (2.00-3.15), and a few others. Additive Bayesian network modeling suggests that age, sex, MHR, and FM/WT are directly associated with MetS and probably affect its manifestation. Additionally, MetS may be causing the GDF-15 and L/A ratio. Our novel findings suggest the existence of complex, age-related, and possibly hierarchical relationships between MetS and factors associated with obesity.
Collapse
Affiliation(s)
- Nader Tarabeih
- Department of Morphological Sciences, Adelson School of Medicine, Ariel University, Ariel 40700, Israel; (N.T.); (S.A.)
| | - Alexander Kalinkovich
- Department of Anatomy and Anthropology, Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel; (A.K.); (S.S.C.)
| | - Shai Ashkenazi
- Department of Morphological Sciences, Adelson School of Medicine, Ariel University, Ariel 40700, Israel; (N.T.); (S.A.)
| | - Stacey S. Cherny
- Department of Anatomy and Anthropology, Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel; (A.K.); (S.S.C.)
| | - Adel Shalata
- The Simon Winter Institute for Human Genetics, Bnai Zion Medical Center, The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 32000, Israel;
| | - Gregory Livshits
- Department of Morphological Sciences, Adelson School of Medicine, Ariel University, Ariel 40700, Israel; (N.T.); (S.A.)
- Department of Anatomy and Anthropology, Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel; (A.K.); (S.S.C.)
| |
Collapse
|
|
12
|
Neagu M, Dobre EG. New Insights into the Link Between Melanoma and Obesity. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1460:851-867. [PMID: 39287874 DOI: 10.1007/978-3-031-63657-8_28] [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
The significant increase in the incidence of obesity represents a global health crisis. Obesity is actually a multi-organ disease affecting the entire organism; hence, skin is no exception. As the functional alterations in the adipose tissue are contributing factors to many diseases, including cancer, recently, the link between the development of melanoma skin cancer and obesity gains increased attention. Besides several other factors, the increase of adipose stromal/stem cells (ASCs) impacts cancer progression. Moreover, increased production of cytokines and growth factors done by ASCs induces tumorigenesis and metastasis. The chronic inflammatory state that is sustained by this metabolic imbalance favors skin malignancies, melanoma included. Cutaneous melanoma, as an aggressive skin cancer, has both intrinsic and extrinsic risk factors where sun exposure and lifestyles are the main environmental factors inducing this skin cancer. With the advent of recent targeted and immune-based therapies in melanoma, the link between obesity and the efficacy of these therapies in melanoma remains controversial. A recent molecular relationship between the melanocortin pathway appending to both melanin synthesis and obesity was established. The biology of adipokines, molecules secreted by the adipose tissue, is linked to inflammation, and their molecular pathways can be involved in angiogenesis, migration, invasion, and proliferation of melanoma cells. In melanoma cells, among the most noticeable metabolic reprogramming characteristics is an increased rate of lipid synthesis. Lipid mediators impact classical oncogenic pathways, affecting melanoma progression. The chapter will tackle also the practical implications for melanoma prevention and treatment, namely, how metabolic manipulation can be exploited to overcome immunosuppression and support immune checkpoint blockade efficacy.
Collapse
Affiliation(s)
- Monica Neagu
- Immunology Laboratory, Victor Babes National Institute of Pathology, Bucharest, Romania
- Pathology Department, Colentina University Hospital, Bucharest, Romania
- Doctoral School of Biology, Faculty of Biology, University of Bucharest, Bucharest, Romania
| | - Elena-Georgiana Dobre
- Immunology Laboratory, Victor Babes National Institute of Pathology, Bucharest, Romania
| |
Collapse
|
|
13
|
Al-Kuraishy HM, Jabir MS, Albuhadily AK, Al-Gareeb AI, Rafeeq MF. The link between metabolic syndrome and Alzheimer disease: A mutual relationship and long rigorous investigation. Ageing Res Rev 2023; 91:102084. [PMID: 37802319 DOI: 10.1016/j.arr.2023.102084] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 10/01/2023] [Accepted: 10/03/2023] [Indexed: 10/08/2023]
Abstract
It has been illustrated that metabolic syndrome (MetS) is associated with Alzheimer disease (AD) neuropathology. Components of MetS including central obesity, hypertension, insulin resistance (IR), and dyslipidemia adversely affect the pathogenesis of AD by different mechanisms including activation of renin-angiotensin system (RAS), inflammatory signaling pathways, neuroinflammation, brain IR, mitochondrial dysfunction, and oxidative stress. MetS exacerbates AD neuropathology, and targeting of molecular pathways in MetS by pharmacological approach could a novel therapeutic strategy in the management of AD in high risk group. However, the underlying mechanisms of these pathways in AD neuropathology are not completely clarified. Therefore, this review aims to elucidate the association between MetS and AD regarding the oxidative and inflammatory mechanistic pathways.
Collapse
Affiliation(s)
- Haydar M Al-Kuraishy
- Department of Clinical pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, Iraq
| | - Majid S Jabir
- Department of Applied science, University of technology, Iraq.
| | - Ali K Albuhadily
- Department of Clinical pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, Iraq
| | - Ali I Al-Gareeb
- Department of Clinical pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, Iraq
| | | |
Collapse
|
|
14
|
Shi R, Chen D, Ji M, Zhou B, Zhang Z, Zhang C, Li M. Network pharmacology-based screening of the active ingredients and mechanisms of Cymbaria daurica against diabetes mellitus. FOOD SCIENCE AND HUMAN WELLNESS 2023. [DOI: 10.1016/j.fshw.2023.03.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
|
|
15
|
Wang H, Wang L, Cheng H, Ge H, Xie Z, Li D. Large yellow tea polysaccharides ameliorate obesity-associated metabolic syndrome by promoting M2 polarization of adipose tissue macrophages. Food Funct 2023; 14:9337-9349. [PMID: 37782075 DOI: 10.1039/d3fo01691a] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/03/2023]
Abstract
Obesity-induced metabolic syndrome is strongly associated with infiltrated adipose tissue macrophages (ATMs). Large yellow tea, a traditional functional beverage in China, has been shown to possess anti-obesity effects. However, the effect of large yellow tea polysaccharides (LYPs) against obesity-associated metabolic syndrome and their underlying mechanisms remain unclear and must be extensively investigated. In this study, we investigated the ameliorative effect of LYPs on metabolic syndrome using a high-fat diet (HFD)-induced obese mouse model. Our results indicated that LYPs significantly alleviated weight gain, dyslipidemia, glucose intolerance, and insulin resistance. Moreover, LYPs restored the homeostasis of energy metabolism and pancreatic β-cell function. Notably, LYPs promoted M2 polarization of ATMs by regulating the expression of genes and specific cytokines involved in the assembly and secretion of M2 polarization. The improved metabolic syndrome of LYPs might be associated with the modulation of macrophage polarization. These findings suggest that LYPs might be a novel potential therapeutic agent to prevent or treat HFD-induced metabolic disorders by regulating M2 polarization.
Collapse
Affiliation(s)
- Hongyan Wang
- State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science and Technology, Anhui Agricultural University, Hefei, Anhui 230036, People's Republic of China.
| | - Lan Wang
- State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science and Technology, Anhui Agricultural University, Hefei, Anhui 230036, People's Republic of China.
| | - Huijun Cheng
- College of Life Sciences, Anhui Agricultural University, Hefei, Anhui 230036, People's Republic of China
| | - Huifang Ge
- State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science and Technology, Anhui Agricultural University, Hefei, Anhui 230036, People's Republic of China.
| | - Zhongwen Xie
- State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science and Technology, Anhui Agricultural University, Hefei, Anhui 230036, People's Republic of China.
| | - Daxiang Li
- State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science and Technology, Anhui Agricultural University, Hefei, Anhui 230036, People's Republic of China.
| |
Collapse
|
|
16
|
Ahmed K, Choi HN, Yim JE. The Impact of Taurine on Obesity-Induced Diabetes Mellitus: Mechanisms Underlying Its Effect. Endocrinol Metab (Seoul) 2023; 38:482-492. [PMID: 37846056 PMCID: PMC10613769 DOI: 10.3803/enm.2023.1776] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 08/07/2023] [Accepted: 08/28/2023] [Indexed: 10/18/2023] Open
Abstract
This review explores the potential benefits of taurine in ameliorating the metabolic disorders of obesity and type 2 diabetes (T2D), highlighting the factors that bridge these associations. Relevant articles and studies were reviewed to conduct a comprehensive analysis of the relationship between obesity and the development of T2D and the effect of taurine on those conditions. The loss of normal β-cell function and development of T2D are associated with obesity-derived insulin resistance. The occurrence of diabetes has been linked to the low bioavailability of taurine, which plays critical roles in normal β-cell function, anti-oxidation, and anti-inflammation. The relationships among obesity, insulin resistance, β-cell dysfunction, and T2D are complex and intertwined. Taurine may play a role in ameliorating these metabolic disorders through different pathways, but further research is needed to fully understand its effects and potential as a therapeutic intervention.
Collapse
Affiliation(s)
- Kainat Ahmed
- Interdisciplinary Program in Senior Human Ecology, Changwon National University, Changwon, Korea
| | - Ha-Neul Choi
- Department of Food and Nutrition, Changwon National University, Changwon, Korea
| | - Jung-Eun Yim
- Interdisciplinary Program in Senior Human Ecology, Changwon National University, Changwon, Korea
- Department of Food and Nutrition, Changwon National University, Changwon, Korea
| |
Collapse
|
|
17
|
Sharifi-Zahabi E, Rezvani N, Hajizadeh-Sharafabad F, Hosseini-Baharanchi FS, Shidfar F, Rahimi M. Theobromine supplementation in combination with a low-calorie diet improves cardiovascular risk factors in overweight and obese subjects with metabolic syndrome: a randomized controlled trial. Food Funct 2023; 14:8431-8441. [PMID: 37615657 DOI: 10.1039/d3fo00555k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/25/2023]
Abstract
Background & aims: The beneficial effects of theobromine (TB) on obesity and features of metabolic syndrome (MetS) have been reported in several studies. However, the findings are equivocal. The present study aimed to investigate the effects of 12 week pure TB supplementation (450 mg day-1) combined with a low-calorie diet on the anthropometric and metabolic syndrome indices in overweight and obese adults with MetS. Methods: In a randomized double-blind parallel controlled trial, 80 participants aged 40-55 years were randomly assigned to take 450 mg day-1 TB or placebo along with a low-calorie diet for 12 weeks. Dietary intake, anthropometric indices, blood pressure, lipid profile and glycemic indices were assessed at the start and end of the intervention. Results: Seventy-two participants completed the study. After 12 weeks, TB supplementation significantly decreased the waist circumference (WC) (-0.86 cm; P = 0.045), LDL-c/HDL-c (-0.26; P = 0.008), TG/HDL-c (-0.41; P = 0.001), TC/HDL-c (-0.38; P = 0.006) and increased HDL-c (1.72 mg dl-1; P = 0.036) compared to the placebo group. There were no significant differences regarding body weight, BMI, hip circumference (HC), hip-to-waist circumference ratio (WHR), systolic and diastolic blood pressure, fasting levels of total cholesterol (TC), triacylglycerol (TAG), low-density lipoprotein cholesterol (LDL-c), fasting blood glucose, insulin, homoeostatic model assessment for insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β) between the two groups (p > 0.05). Conclusion: The results of the current study revealed that TB supplementation along with a low-calorie diet had favorable effects on WC, LDL-c/HDL-c, TG/HDL-c, TC/HDL-c, and serum level of HDL-c in overweight and obese subjects with MetS. Trial registration number: IRCT20091114002709N59. Registration date: 5 March 2022.
Collapse
Affiliation(s)
- Elham Sharifi-Zahabi
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Nayebali Rezvani
- Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | | | - Fatemeh Sadat Hosseini-Baharanchi
- Minimally Invasive Surgery Research Center, & Department of Biostatistics, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Farzad Shidfar
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.
| | - Mehrali Rahimi
- School of Medicine, Diabetic Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| |
Collapse
|
|
18
|
Sharifi-Zahabi E, Hajizadeh-Sharafabad F, Nachvak SM, Mirzaian S, Darbandi S, Shidfar F. A comprehensive insight into the molecular effect of theobromine on cardiovascular-related risk factors: A systematic review of in vitro and in vivo studies. Phytother Res 2023; 37:3765-3779. [PMID: 37309834 DOI: 10.1002/ptr.7916] [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: 10/16/2022] [Revised: 05/11/2023] [Accepted: 05/27/2023] [Indexed: 06/14/2023]
Abstract
Theobromine may have beneficial effects on cardiovascular risk factors. This study aimed to find molecular effects of theobromine on lipid profile, glycemic status, inflammatory factors, and vascular function through a comprehensive assessment of all in vitro and in vivo studies. The search process was started at 18 July 2022. Databases including PubMed, Scopus, and Web of Science were searched to find all articles published up to 18 July 2022. Nineteen studies were included in this study. In vitro studies showed the improving effects of theobromine on inflammatory markers. Of four animal studies assessing the effect of theobromine on inflammatory markers, two reported favorable effects. Among five animal studies assessing the effects of theobromine on lipid profile, three reported improving effects on either triglyceride, total cholesterol, low- or high-density lipoprotein cholesterol. Of the three human studies, two revealed that theobromine had improving effects on lipid profile. A favorable effect of theobromine on augmentation index was also reported in two RCTs. The results for other outcomes were inconclusive. Theobromine may have favorable effects on inflammatory factors, lipid profile, and vascular function markers. However, studies with a longer duration and lower, dietary-relevant doses are required for future confirmation.
Collapse
Affiliation(s)
| | | | - Seyed Mostafa Nachvak
- School of Nutritional Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Soheila Mirzaian
- Department of Food and Human Nutrition Sciences, University of Manitoba, Winnipeg, Canada
| | - Sahar Darbandi
- Imam Khomeini comprehensive health center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Farzad Shidfar
- Department of nutrition, School of public health, Iran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
19
|
Abstract
In this review, we provide a brief synopsis of the connections between adipose tissue and metabolic health and highlight some recent developments in understanding and exploiting adipocyte biology. Adipose tissue plays critical roles in the regulation of systemic glucose and lipid metabolism and secretes bioactive molecules possessing endocrine, paracrine, and autocrine functions. Dysfunctional adipose tissue has a detrimental impact on metabolic health and is intimately involved in key aspects of metabolic diseases such as insulin resistance, lipid overload, inflammation, and organelle stress. Differences in the distribution of fat depots and adipose characteristics relate to divergent degrees of metabolic dysfunction found in metabolically healthy and unhealthy obese individuals. Thermogenic adipocytes increase energy expenditure via mitochondrial uncoupling or adenosine triphosphate-consuming futile substrate cycles, while functioning as a metabolic sink and participating in crosstalk with other metabolic organs. Manipulation of adipose tissue provides a wealth of opportunities to intervene and combat the progression of associated metabolic diseases. We discuss current treatment modalities for obesity including incretin hormone analogs and touch upon emerging strategies with therapeutic potential including exosome-based therapy, pharmacological activation of brown and beige adipocyte thermogenesis, and administration or inhibition of adipocyte-derived factors.
Collapse
Affiliation(s)
- Sung-Min An
- Division of Endocrinology, Department of Internal Medicine, University of California Davis School of Medicine, Davis, CA, USA
| | - Seung-Hee Cho
- Division of Endocrinology, Department of Internal Medicine, University of California Davis School of Medicine, Davis, CA, USA
| | - John C. Yoon
- Division of Endocrinology, Department of Internal Medicine, University of California Davis School of Medicine, Davis, CA, USA
| |
Collapse
|
|
20
|
Mukherjee S, Skrede S, Haugstøyl M, López M, Fernø J. Peripheral and central macrophages in obesity. Front Endocrinol (Lausanne) 2023; 14:1232171. [PMID: 37720534 PMCID: PMC10501731 DOI: 10.3389/fendo.2023.1232171] [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: 05/31/2023] [Accepted: 07/28/2023] [Indexed: 09/19/2023] Open
Abstract
Obesity is associated with chronic, low-grade inflammation. Excessive nutrient intake causes adipose tissue expansion, which may in turn cause cellular stress that triggers infiltration of pro-inflammatory immune cells from the circulation as well as activation of cells that are residing in the adipose tissue. In particular, the adipose tissue macrophages (ATMs) are important in the pathogenesis of obesity. A pro-inflammatory activation is also found in other organs which are important for energy metabolism, such as the liver, muscle and the pancreas, which may stimulate the development of obesity-related co-morbidities, including insulin resistance, type 2 diabetes (T2D), cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD). Interestingly, it is now clear that obesity-induced pro-inflammatory signaling also occurs in the central nervous system (CNS), and that pro-inflammatory activation of immune cells in the brain may be involved in appetite dysregulation and metabolic disturbances in obesity. More recently, it has become evident that microglia, the resident macrophages of the CNS that drive neuroinflammation, may also be activated in obesity and can be relevant for regulation of hypothalamic feeding circuits. In this review, we focus on the action of peripheral and central macrophages and their potential roles in metabolic disease, and how macrophages interact with other immune cells to promote inflammation during obesity.
Collapse
Affiliation(s)
- Sayani Mukherjee
- Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
- Mohn Center for Diabetes Precision Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway
- Department of Physiology, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
| | - Silje Skrede
- Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway
- Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
| | - Martha Haugstøyl
- Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
- Mohn Center for Diabetes Precision Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Miguel López
- Department of Physiology, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
| | - Johan Fernø
- Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
- Mohn Center for Diabetes Precision Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway
| |
Collapse
|
|
21
|
Li X, Zhou B, Wu Z, Li Y, Meng H. Role of Growth Hormone in Adipose Tissue Insulin Resistance Amelioration After Bariatric Surgery in Adults with Obesity. Metab Syndr Relat Disord 2023; 21:345-352. [PMID: 37347960 DOI: 10.1089/met.2023.0034] [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: 06/24/2023] Open
Abstract
Background: Bariatric surgery has a significant effect on weight loss and improves adipose tissue insulin resistance (adipose-IR); however, the underlying mechanism remains unclear. This study aimed to investigate the effect of growth hormone (GH) on adipose-IR improvement after bariatric surgery in patients with obesity. Methods: A prospective cohort study with 1-year follow-up was conducted in the China-Japan Friendship Hospital. Pre- and postoperative variables, including the body mass index (BMI), glucose and lipid metabolic indicators, and the adipose-IR index, were collected and analyzed at baseline and 3, 6, and 12 months after surgery in patients with obesity. Results: In total, seventy-two patients, including 25 males and 47 females, were included in the analysis. Furthermore, bariatric surgery resulted in a sharp decline in BMI (kg/m2) (from 39.45 ± 0.51 to 32.00 ± 0.63 at 3 months, 28.73 ± 0.56 at 6 months, and 27.25 ± 0.68 at 12 months) and adipose-IR index (mmol/L × pmol/L) (from 163.8 ± 9.38 to 94.39 ± 16.63, 43.71 ± 5.13, and 27.92 ± 2.67) and an increase in GH (ng/mL) (from 0.16 ± 0.02 to 0.61 ± 0.10, 1.02 ± 0.19, and 0.89 ± 0.20). Partial correlation analyses were performed with reduced BMI as a control, and elevated GH levels (ΔGH) were found to be positively correlated with reduced adipose-IR (absolute value of Δadipose-IR) index at 3 months (r = 0.413, P = 0.005), 6 months (r = 0.432, P < 0.001), and 12 months (r = 0.375, P = 0.031) after bariatric surgery. Conclusions: Bariatric surgery induces GH elevation and adipose-IR amelioration in patients with obesity. GH might be a potential metabolic regulator associated with adipose-IR improvement in patients with obesity after bariatric surgery.
Collapse
Affiliation(s)
- Xiaohui Li
- Department of Endocrinology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Biao Zhou
- Department of General Surgery & Obesity and Metabolic Disease Center, China-Japan Friendship Hospital, Beijing, China
| | - Zhenyu Wu
- Department of Endocrinology, Beijing Daxing District People's Hospital, Beijing, China
| | - Yinhui Li
- Department of Endocrinology, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, China
| | - Hua Meng
- Department of General Surgery & Obesity and Metabolic Disease Center, China-Japan Friendship Hospital, Beijing, China
| |
Collapse
|
|
22
|
Todosenko N, Khaziakhmatova O, Malashchenko V, Yurova K, Bograya M, Beletskaya M, Vulf M, Mikhailova L, Minchenko A, Soroko I, Khlusov I, Litvinova L. Adipocyte- and Monocyte-Mediated Vicious Circle of Inflammation and Obesity (Review of Cellular and Molecular Mechanisms). Int J Mol Sci 2023; 24:12259. [PMID: 37569635 PMCID: PMC10418857 DOI: 10.3390/ijms241512259] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 07/26/2023] [Accepted: 07/27/2023] [Indexed: 08/13/2023] Open
Abstract
Monocytes play a key role in the development of metabolic syndrome, and especially obesity. Given the complex features of their development from progenitor cells, whose regulation is mediated by their interactions with bone marrow adipocytes, the importance of a detailed study of the heterogeneous composition of monocytes at the molecular and systemic levels becomes clear. Research argues for monocytes as indicators of changes in the body's metabolism and the possibility of developing therapeutic strategies to combat obesity and components of metabolic syndrome based on manipulations of the monocyte compound of the immune response. An in-depth study of the heterogeneity of bone-marrow-derived monocytes and adipocytes could provide answers to many questions about the pathogenesis of obesity and reveal their therapeutic potential.
Collapse
Affiliation(s)
- Natalia Todosenko
- Center for Immunology and Cellular Biotechnology, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, Russia; (N.T.); (O.K.); (V.M.); (K.Y.); (M.B.); (M.B.); (M.V.); (L.M.); (A.M.); (I.S.); (I.K.)
| | - Olga Khaziakhmatova
- Center for Immunology and Cellular Biotechnology, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, Russia; (N.T.); (O.K.); (V.M.); (K.Y.); (M.B.); (M.B.); (M.V.); (L.M.); (A.M.); (I.S.); (I.K.)
| | - Vladimir Malashchenko
- Center for Immunology and Cellular Biotechnology, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, Russia; (N.T.); (O.K.); (V.M.); (K.Y.); (M.B.); (M.B.); (M.V.); (L.M.); (A.M.); (I.S.); (I.K.)
| | - Kristina Yurova
- Center for Immunology and Cellular Biotechnology, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, Russia; (N.T.); (O.K.); (V.M.); (K.Y.); (M.B.); (M.B.); (M.V.); (L.M.); (A.M.); (I.S.); (I.K.)
| | - Maria Bograya
- Center for Immunology and Cellular Biotechnology, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, Russia; (N.T.); (O.K.); (V.M.); (K.Y.); (M.B.); (M.B.); (M.V.); (L.M.); (A.M.); (I.S.); (I.K.)
| | - Maria Beletskaya
- Center for Immunology and Cellular Biotechnology, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, Russia; (N.T.); (O.K.); (V.M.); (K.Y.); (M.B.); (M.B.); (M.V.); (L.M.); (A.M.); (I.S.); (I.K.)
| | - Maria Vulf
- Center for Immunology and Cellular Biotechnology, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, Russia; (N.T.); (O.K.); (V.M.); (K.Y.); (M.B.); (M.B.); (M.V.); (L.M.); (A.M.); (I.S.); (I.K.)
| | - Larisa Mikhailova
- Center for Immunology and Cellular Biotechnology, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, Russia; (N.T.); (O.K.); (V.M.); (K.Y.); (M.B.); (M.B.); (M.V.); (L.M.); (A.M.); (I.S.); (I.K.)
| | - Anastasia Minchenko
- Center for Immunology and Cellular Biotechnology, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, Russia; (N.T.); (O.K.); (V.M.); (K.Y.); (M.B.); (M.B.); (M.V.); (L.M.); (A.M.); (I.S.); (I.K.)
| | - Irina Soroko
- Center for Immunology and Cellular Biotechnology, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, Russia; (N.T.); (O.K.); (V.M.); (K.Y.); (M.B.); (M.B.); (M.V.); (L.M.); (A.M.); (I.S.); (I.K.)
| | - Igor Khlusov
- Center for Immunology and Cellular Biotechnology, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, Russia; (N.T.); (O.K.); (V.M.); (K.Y.); (M.B.); (M.B.); (M.V.); (L.M.); (A.M.); (I.S.); (I.K.)
- Laboratory of Cellular and Microfluidic Technologies, Siberian State Medical University, 2, Moskovskii Trakt, 634050 Tomsk, Russia
| | - Larisa Litvinova
- Center for Immunology and Cellular Biotechnology, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, Russia; (N.T.); (O.K.); (V.M.); (K.Y.); (M.B.); (M.B.); (M.V.); (L.M.); (A.M.); (I.S.); (I.K.)
- Laboratory of Cellular and Microfluidic Technologies, Siberian State Medical University, 2, Moskovskii Trakt, 634050 Tomsk, Russia
| |
Collapse
|
|
23
|
Adipose tissue macrophages and their role in obesity-associated insulin resistance: an overview of the complex dynamics at play. Biosci Rep 2023; 43:232519. [PMID: 36718668 PMCID: PMC10011338 DOI: 10.1042/bsr20220200] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 01/18/2023] [Accepted: 01/26/2023] [Indexed: 02/01/2023] Open
Abstract
Obesity, a major global health concern, is characterized by serious imbalance between energy intake and expenditure leading to excess accumulation of fat in adipose tissue (AT). A state of chronic low-grade AT inflammation is prevalent during obesity. The adipose tissue macrophages (ATM) with astounding heterogeneity and complex regulation play a decisive role in mediating obesity-induced insulin resistance. Adipose-derived macrophages were broadly classified as proinflammatory M1 and anti-inflammatory M2 subtypes but recent reports have proclaimed several novel and intermediate profiles, which are crucial in understanding the dynamics of macrophage phenotypes during development of obesity. Lipid-laden hypertrophic adipocytes release various chemotactic signals that aggravate macrophage infiltration into AT skewing toward mostly proinflammatory status. The ratio of M1-like to M2-like macrophages is increased substantially resulting in copious secretion of proinflammatory mediators such as TNFα, IL-6, IL-1β, MCP-1, fetuin-A (FetA), etc. further worsening insulin resistance. Several AT-derived factors could influence ATM content and activation. Apart from being detrimental, ATM exerts beneficial effects during obesity. Recent studies have highlighted the prime role of AT-resident macrophage subpopulations in not only effective clearance of excess fat and dying adipocytes but also in controlling vascular integrity, adipocyte secretions, and fibrosis within obese AT. The role of ATM subpopulations as friend or foe is determined by an intricate interplay of such factors arising within hyperlipidemic microenvironment of obese AT. The present review article highlights some of the key research advances in ATM function and regulation, and appreciates the complex dynamics of ATM in the pathophysiologic scenario of obesity-associated insulin resistance.
Collapse
|
|
24
|
Pan J, Yin J, Gan L, Xue J. Two-sided roles of adipose tissue: Rethinking the obesity paradox in various human diseases from a new perspective. Obes Rev 2023; 24:e13521. [PMID: 36349390 DOI: 10.1111/obr.13521] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 08/05/2022] [Accepted: 10/17/2022] [Indexed: 11/11/2022]
Abstract
Overweight and obesity, as a result of excess fat accumulation, have become a worldwide public health issue. Recent studies have shown that obesity is closely related to many human diseases, such as cancer, cardiovascular diseases, and type 2 diabetes mellitus, in which adipose tissue plays a dual role. In addition to thermal and mechanical insulation and a critical role in energy storage and heat production, adipose tissue is also a highly plastic endocrine and signaling organ that secretes multiple bioactive molecules for inter-organ crosstalk. The phenotypic and biological changes of adipose tissue under pathological conditions, especially in obesity, increase the challenge of deciphering the positive or negative effects of adipose tissue in disease. Despite numerous studies on obesity and adipose tissue, the ambiguous role of adipose tissue on specific organs or tissues in different diseases is not fully understood, and the definite mechanisms remain obscure. In this review, we first summarize the basic biological characteristics of adipose tissue in the physiological state and the abnormal remodeling of adipose tissue during obesity. We then discuss the complex and disparate effects of obesity on various human diseases, with a particular focus on the dual roles and underlying mechanisms of adipose tissue, a quintessential player in obesity, in this process. More importantly, rethinking the causes of the "obesity paradox" phenomenon in diseases from the perspective of adipose homeostasis and dysfunction provides a novel strategy for disease treatment by intervening in fat function.
Collapse
Affiliation(s)
- Jing Pan
- Thoracic Oncology Ward, Cancer Center and State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Jianqiong Yin
- Thoracic Oncology Ward, Cancer Center and State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Lu Gan
- Research Laboratory of Emergency Medicine, Department of Emergency Medicine, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Jianxin Xue
- Thoracic Oncology Ward, Cancer Center and State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.,Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.,Laboratory of Clinical Cell Therapy, West China Hospital, Sichuan University, Chengdu, China
| |
Collapse
|
|
25
|
Inflammaging and body composition: New insights in diabetic and hypertensive elderly men. Exp Gerontol 2022; 170:112005. [PMID: 36341786 DOI: 10.1016/j.exger.2022.112005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 10/24/2022] [Accepted: 10/25/2022] [Indexed: 12/29/2022]
Abstract
Age-related changes in the body's physiological responses play a critical role in systemic arterial hypertension (SAH) and type 2 Diabetes mellitus (T2DM). SAH and T2DM have clinically silent low-grade inflammation as a common risk factor. This inflammation has a relevant element, the excess of fatty tissue. In this scenario, little is known about how inflammatory markers interact with each other. Therefore, this work evaluated the interplay among anthropometric, biochemical, and inflammatory markers in the elderly with SAH and T2DM. Men aged 60-80 years old with SAH and T2DM were classified by body mass index (BMI) as eutrophic elderly (EE, 24 individuals) or overweight elderly (OE, 25 individuals). Body composition analysis was performed using bioimpedance. Blood samples were collected to perform inflammatory and biochemical evaluations. The cytokines IL-17A, IL-1β, IFN-y, TNF-α, and IL-10, were evaluated by ELISA. Triglycerides, total and fractions of cholesterol, and glucose were measured by spectrophotometry. Overweight elderly men had a higher glycemic index and an increase in most anthropometric markers, as well as higher means for all pro-inflammatory cytokines analyzed (IL-17A, IL-1β, IFN-y, and TNF-α) in comparison to their eutrophic elderly counterparts. However, there was a decrease in IL-10 anti-inflammatory cytokine and IL-10/IL-17A ratio compared to their eutrophic elderly counterparts. Although overweight elderly men have worsening inflammatory parameters, the magnitude of their correlations with anthropometric and biochemical parameters becomes less evident. The Bayesian networks highlight that in the eutrophic elderly, IL-17A and TNF-α are the cytokines most associated with interactions, and most of these interactions occur with biochemical parameters. It is worth highlighting the role of IFN-y in overweight elderly men. This cytokine influences IL-10 and TNF-α production, contributing to the inflammatory profile exacerbated in this group.
Collapse
|
|
26
|
Jang M, Choi SI. Schisandrin C isolated from Schisandra chinensis fruits inhibits lipid accumulation by regulating adipogenesis and lipolysis through AMPK signaling in 3T3-L1 adipocytes. J Food Biochem 2022; 46:e14454. [PMID: 36200699 DOI: 10.1111/jfbc.14454] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 09/05/2022] [Accepted: 09/16/2022] [Indexed: 01/14/2023]
Abstract
In this study, lignans of Schisandra chinensis fruits (SCF) were profiled using HPLC-MS/MS, and the inhibitory effects of nine of these lignans were evaluated on triglyceride (TG) accumulation. We then examined the effects and molecular mechanisms on adipogenesis and lipolysis of schisandrin C (SC), which most inhibited TG levels during adipogenesis of 3T3-L1 cells. Treatment of 3T3-L1 cells with SC markedly decreased adipocyte differentiation but did not influence cell proliferation. During adipogenesis, SC significantly reduced total lipid and TG contents and down-regulated the mRNA expressions of C/EBPα, PPARγ, SREBP1c, aP2, and FAS. In addition, SC significantly increased p-AMPK, and this activation regulated the protein levels of major adipogenic transcription factors (PPARγ and C/EBPα). Furthermore, SC lowered the mRNA expressions of HSL and perilipin and inhibited pancreatic lipase levels, which are both related to lipolysis. PRACTICAL APPLICATIONS: Our results indicate that SC regulates lipogenesis and lipolysis by increasing AMPK phosphorylation and suggest that it may be beneficial for preventing obesity and related metabolic diseases. Thus, this study proposes a mechanical basis for developing SC-containing foods as a beneficial dietary strategy.
Collapse
Affiliation(s)
- Miran Jang
- Department of Food and Life Science, Inje University, Gimhae, South Korea
| | - Soo-Im Choi
- Department of Health Functional New Materials, Duksung Women's University, Seoul, South Korea.,MEDIOGEN Co., Ltd. R&D center, Jecheon, South Korea
| |
Collapse
|
|
27
|
Ryyti R, Hämäläinen M, Leppänen T, Peltola R, Moilanen E. Phenolic Compounds Known to Be Present in Lingonberry ( Vaccinium vitis-idaea L.) Enhance Macrophage Polarization towards the Anti-Inflammatory M2 Phenotype. Biomedicines 2022; 10:3045. [PMID: 36551801 PMCID: PMC9776286 DOI: 10.3390/biomedicines10123045] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Revised: 11/10/2022] [Accepted: 11/15/2022] [Indexed: 11/29/2022] Open
Abstract
Macrophages are pleiotropic immune cells whose phenotype can polarize towards the pro-inflammatory M1 or anti-inflammatory M2 direction as a response to environmental changes. In obesity, the number of macrophages in adipose tissue is enhanced, and they shift towards the M1 phenotype. Activated M1 macrophages secrete pro-inflammatory cytokines and adipokines involved in the development of systemic low-grade inflammation, complicating obesity. Polyphenols are widely found in the vegetable kingdom and have anti-inflammatory properties. We and others have recently found that lingonberry (Vaccinium vitis-idaea L.) supplementation is able to prevent the development of low-grade inflammation and its metabolic consequences in experimentally induced obesity. In the present study, we investigated the effects of twelve phenolic compounds known to be present in lingonberry (resveratrol, piceid, quercetin, kaempferol, proanthocyanidins, delphinidin, cyanidin, benzoic acid, cinnamic acid, coumaric acid, caffeic acid, and ferulic acid) on macrophage polarization, which is a meaningful mechanism determining the low-grade inflammation in obesity. Mouse J774 and human U937 macrophages and commercially available phenolic compounds were used in the studies. Three of the twelve compounds investigated showed an effect on macrophage polarization. Resveratrol, kaempferol, and proanthocyanidins enhanced anti-inflammatory M2-type activation, evidenced as increased expression of Arg-1 and MRC-1 in murine macrophages and CCL-17 and MRC-1 in human macrophages. Resveratrol and kaempferol also inhibited pro-inflammatory M1-type activation, shown as decreased expression of IL-6, NO, and MCP-1 in murine macrophages and TNF-α and IL-6 in human macrophages. In the further mechanistic studies, the effects of the three active compounds were investigated on two transcription factors important in M2 activation, namely on PPARγ and STAT6. Resveratrol and kaempferol were found to enhance PPARγ expression, while proanthocyanidins increased the phosphorylation of STAT6. The results suggest proanthocyanidins, resveratrol, and kaempferol as active constituents that may be responsible for the positive anti-inflammatory effects of lingonberry supplementation in obesity models. These data also extend the previous knowledge on the anti-inflammatory effects of lingonberry and encourage further studies to support the use of lingonberry and lingonberry-based products as a part of a healthy diet.
Collapse
Affiliation(s)
- Riitta Ryyti
- The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University Hospital, Tampere University, 33014 Tampere, Finland
| | - Mari Hämäläinen
- The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University Hospital, Tampere University, 33014 Tampere, Finland
| | - Tiina Leppänen
- The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University Hospital, Tampere University, 33014 Tampere, Finland
| | - Rainer Peltola
- Bioeconomy and Environment, Natural Resources Institute Finland, 96200 Rovaniemi, Finland
| | - Eeva Moilanen
- The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University Hospital, Tampere University, 33014 Tampere, Finland
| |
Collapse
|
|
28
|
van der Valk ES, Mulder DS, Kouwenhoven T, Nagtzaam NMA, van Rossum EFC, Dik WA, Leenen PJM. Monocyte adaptations in patients with obesity during a 1.5 year lifestyle intervention. Front Immunol 2022; 13:1022361. [PMID: 36466916 PMCID: PMC9716348 DOI: 10.3389/fimmu.2022.1022361] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 10/28/2022] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Obesity is associated with chronic, low-grade inflammation, which is reflected in altered peripheral blood monocyte characteristics. The aim of this study was to analyze the monocyte subset composition (classical (CM), intermediate (IM) and non-classical monocytes (NCM)), and their inflammatory marker profile (CD14, CD16, CD36, CD45, CD64, CD300e, HLA-DR) in individuals with obesity during a 1.5 year combined lifestyle intervention (CLI), comprising healthy nutrition, increased exercise and behavioral changes. METHODS We analyzed monocyte subset counts and immunophenotypes in 73 individuals with obesity, and associated these to baseline body mass index (BMI) and waist circumference (WC). The measurements were repeated after 10 weeks and at the end of the intervention (1.5 years). RESULTS Generally, monocyte subset counts were not associated to BMI or WC at baseline, neither did monocyte counts change during the 1.5 year CLI. Immunophenotypically, higher baseline BMI and WC were associated to lower CD14 and higher CD300e expression by all subsets. During CLI there were remarkable changes in marker profiles: expression of CD14, CD36, CD45 and CD64 significantly decreased in CM and IM, as did CD16 (IM and NCM) (p<0.05). CD300e initially decreased after 10 weeks, but increased sharply at 1.5 years (all subsets). We observed no consistent associations between changes in monocyte characteristics and anthropometric changes. CONCLUSION A 1.5 year CLI in individuals with obesity mediates persistent immunophenotypic adaptations related to cellular activation in blood monocytes, whereas changes in subset distribution are limited. Lifestyle-induced changes in the inflammatory profile of monocytes differ from the 'less-severe-obesity'-phenotype, suggesting a novel, 'post-weight-loss' monocyte setpoint.
Collapse
Affiliation(s)
- Eline S. van der Valk
- Obesity Center Centrum Gezond Gewicht (CGG), Erasmus Medical Center (MC), University Medical Center Rotterdam, Rotterdam, Netherlands
- Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center (MC), Rotterdam, Netherlands
| | - Daniël S. Mulder
- Obesity Center Centrum Gezond Gewicht (CGG), Erasmus Medical Center (MC), University Medical Center Rotterdam, Rotterdam, Netherlands
- Department of Immunology, Erasmus Medical Center (MC), University Medical Center Rotterdam, Rotterdam, Netherlands
| | - Tessa Kouwenhoven
- Obesity Center Centrum Gezond Gewicht (CGG), Erasmus Medical Center (MC), University Medical Center Rotterdam, Rotterdam, Netherlands
- Laboratory Medical Immunology, Department of Immunology, Erasmus Medical Center (MC), University Medical Center Rotterdam, Rotterdam, Netherlands
| | | | - Elisabeth F. C. van Rossum
- Obesity Center Centrum Gezond Gewicht (CGG), Erasmus Medical Center (MC), University Medical Center Rotterdam, Rotterdam, Netherlands
| | - Willem A. Dik
- Laboratory Medical Immunology, Department of Immunology, Erasmus Medical Center (MC), University Medical Center Rotterdam, Rotterdam, Netherlands
| | - Pieter J. M. Leenen
- Department of Immunology, Erasmus Medical Center (MC), University Medical Center Rotterdam, Rotterdam, Netherlands
| |
Collapse
|
|
29
|
Ni Y, Zhuge F, Ni L, Nagata N, Yamashita T, Mukaida N, Kaneko S, Ota T, Nagashimada M. CX3CL1/CX3CR1 interaction protects against lipotoxicity-induced nonalcoholic steatohepatitis by regulating macrophage migration and M1/M2 status. Metabolism 2022; 136:155272. [PMID: 35914622 DOI: 10.1016/j.metabol.2022.155272] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 07/12/2022] [Accepted: 07/26/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND AND OBJECTIVES Chemokine (C-X3-C motif) ligand 1 (CX3CL1) and its receptor CX3CR1 regulate the migration and activation of immune cells and are involved in the pathogenesis of nonalcoholic steatohepatitis (NASH), but the mechanism remains elusive. Here, the roles of CX3CL1/CX3CR1 in the macrophage migration and polarization in the livers of NASH mice were investigated. METHODS AND RESULTS The expression of Cx3cl1 and Cx3cr1 was markedly upregulated in the livers of lipotoxicity-induced NASH mice. CX3CR1 was predominantly expressed by F4/80+ macrophages and to a lesser degree by hepatic stellate cells or endothelial cells in the livers of NASH mice. Flow cytometry analysis revealed that, compared with chow-fed mice, NASH mice exhibited a significant increase in CX3CR1+ expression by liver macrophages (LMs), particularly M1 LMs. CX3CR1 deficiency caused a significant increase in inflammatory monocyte/macrophage infiltration and a shift toward M1 dominant macrophages in the liver, thereby exacerbating the progression of NASH. Moreover, transplantation of Cx3cr1-/- bone marrow was sufficient to cause glucose intolerance, inflammation, and fibrosis in the liver. In addition, deletion of CCL2 in Cx3cr1-/- mice alleviated NASH progression by decreasing macrophage infiltration and inducing a shift toward M2 dominant LMs. Importantly, overexpression of CX3CL1 in vivo protected against hepatic fibrosis in NASH. CONCLUSION Pharmacological therapy targeting liver CX3CL1/CX3CR1 signaling might be a candidate for the treatment of NASH.
Collapse
Affiliation(s)
- Yinhua Ni
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, China; Department of Cell Metabolism and Nutrition, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan.
| | - Fen Zhuge
- Department of Cell Metabolism and Nutrition, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan; Institute of Translational Medicine, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, China
| | - Liyang Ni
- Food Biochemistry Laboratory, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan
| | - Naoto Nagata
- Department of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan
| | - Tatsuya Yamashita
- Department of Cell Metabolism and Nutrition, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan; Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Ishikawa 920-8641, Japan
| | - Naofumi Mukaida
- Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan
| | - Shuichi Kaneko
- Department of Cell Metabolism and Nutrition, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan
| | - Tsuguhito Ota
- Department of Cell Metabolism and Nutrition, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan
| | - Mayumi Nagashimada
- Department of Cell Metabolism and Nutrition, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan; Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, Ishikawa 920-8640, Japan.
| |
Collapse
|
|
30
|
Wang H, Xu S, Li D, Xie Z. Structural Characterization and Macrophage Polarization-Modulating Activity of a Novel Polysaccharide from Large Yellow Tea. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:12565-12576. [PMID: 36154025 DOI: 10.1021/acs.jafc.2c05593] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
A novel homogeneous polysaccharide (LYP-S3) that promotes the M2 polarization of macrophages was obtained from large yellow tea by a bioactivity-guided sequential isolation procedure and activity evaluation in the present study. Structural characterization revealed that LYP-S3 has an average molecular weight of 28.6 kDa and is composed of rhamnose, arabinose, galactose, glucose, and galacturonic acid at the molar ratio of 8.08:11.66:11.77:3.96:58.02. The main backbone of LYP-S3 consists of →4)-α-d-GalpA-6-OMe-(1→, β-d-GalpA-(1→, →4)-β-d-Galp-(→1, and →β-d-Galp-(1→, and the branches are composed of α-l-Araf-(→1, →5)-α-l-Araf-(1→, →2,4)-β-l-Rhap-(1→, →2)-β-l-Rhap-(1→, and →4)-β-d-Glcp-(1→. An in vitro bioactivity evaluation assay showed that LYP-S3 remarkably reduced the expression of M1 macrophage markers and increased the expression of M2 macrophage markers. In addition, LYP-S3 inhibited adipocyte differentiation and adipogenesis in 3T3-L1 adipocytes and blocked macrophage migration toward 3T3-L1 adipocytes in the cocultures of bone-marrow-derived monocytes and 3T3-L1 adipocytes. Furthermore, LYP-S3 promoted the M2 polarization of macrophages in cocultures. These findings suggested that LYP-S3 has a potential function in preventing inflammation and obesity.
Collapse
Affiliation(s)
- Hongyan Wang
- State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science and Technology, Anhui Agricultural University, Hefei, Anhui 230036, China
| | - Shan Xu
- State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science and Technology, Anhui Agricultural University, Hefei, Anhui 230036, China
| | - Daxiang Li
- State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science and Technology, Anhui Agricultural University, Hefei, Anhui 230036, China
| | - Zhongwen Xie
- State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science and Technology, Anhui Agricultural University, Hefei, Anhui 230036, China
| |
Collapse
|
|
31
|
How Curcumin Targets Inflammatory Mediators in Diabetes: Therapeutic Insights and Possible Solutions. Molecules 2022; 27:molecules27134058. [PMID: 35807304 PMCID: PMC9268477 DOI: 10.3390/molecules27134058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 06/14/2022] [Accepted: 06/20/2022] [Indexed: 12/15/2022] Open
Abstract
Diabetes mellitus is a multifactorial chronic metabolic disorder, characterized by altered metabolism of macro-nutrients, such as fats, proteins, and carbohydrates. Diabetic retinopathy, diabetic cardiomyopathy, diabetic encephalopathy, diabetic periodontitis, and diabetic nephropathy are the prominent complications of diabetes. Inflammatory mediators are primarily responsible for these complications. Curcumin, a polyphenol derived from turmeric, is well known for its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. The regulation of several signaling pathways effectively targets inflammatory mediators in diabetes. Curcumin’s anti-inflammatory and anti-oxidative activities against a wide range of molecular targets have been shown to have therapeutic potential for a variety of chronic inflammatory disorders, including diabetes. Curcumin’s biological examination has shown that it is a powerful anti-oxidant that stops cells from growing by releasing active free thiol groups at the target location. Curcumin is a powerful anti-inflammatory agent that targets inflammatory mediators in diabetes, and its resistant form leads to better therapeutic outcomes in diabetes complications. Moreover, Curcumin is an anti-oxidant and NF-B inhibitor that may be useful in treating diabetes. Curcumin has been shown to inhibit diabetes-related enzymes, such as a-glucosidase, aldose reductase and aldose reductase inhibitors. Through its anti-oxidant and anti-inflammatory effects, and its suppression of vascular endothelial development and nuclear transcription factors, curcumin has the ability to prevent, or reduce, the course of diabetic retinopathy. Curcumin improves insulin sensitivity by suppressing phosphorylation of ERK/JNK in HG-induced insulin-resistant cells and strengthening the PI3K-AKT-GSK3B signaling pathway. In the present article, we aimed to discuss the anti-inflammatory mechanisms of curcumin in diabetes regulated by various molecular signaling pathways.
Collapse
|
|
32
|
Tan Y, Chen L, Li K, Lou B, Liu Y, Liu Z. Yeast as carrier for drug delivery and vaccine construction. J Control Release 2022; 346:358-379. [PMID: 35483637 DOI: 10.1016/j.jconrel.2022.04.032] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 04/19/2022] [Accepted: 04/19/2022] [Indexed: 12/16/2022]
Abstract
Yeast has been employed as an effective derived drug carrier as a unicellular microorganism. Many research works have been devoted to the encapsulation of nucleic acid compounds, insoluble small molecule drugs, small molecules, liposomes, polymers, and various nanoparticles in yeast for the treatment of disease. Recombinant yeast-based vaccine carriers (WYV) have played a major role in the development of vaccines. Herein, the latest reports on the application of yeast carriers and the development of related research are summarized, a conceptual description of gastrointestinal absorption of yeast carriers, as well as the various package forms of different drug molecules and nanoparticles in yeast carriers are introduced. In addition, the advantages and development of recombinant yeast vaccine carriers for the disease, veterinary and aquaculture applications are discussed. Moreover, the current challenges and future directions of yeast carriers are proposed.
Collapse
Affiliation(s)
- Yifu Tan
- Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, Hunan Province, PR China
| | - Liwei Chen
- Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, Hunan Province, PR China
| | - Ke Li
- Department of Pharmaceutics, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, Hunan Province, PR China
| | - Beibei Lou
- Department of Pharmaceutics, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, Hunan Province, PR China
| | - Yanfei Liu
- Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, Hunan Province, PR China.
| | - Zhenbao Liu
- Department of Pharmaceutics, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, Hunan Province, PR China; Molecular Imaging Research Center of Central South University, Changsha 410008, Hunan, PR China.
| |
Collapse
|
|
33
|
Wang YY, Wang YD, Qi XY, Liao ZZ, Mai YN, Xiao XH. Organokines and Exosomes: Integrators of Adipose Tissue Macrophage Polarization and Recruitment in Obesity. Front Endocrinol (Lausanne) 2022; 13:839849. [PMID: 35273574 PMCID: PMC8902818 DOI: 10.3389/fendo.2022.839849] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 01/24/2022] [Indexed: 12/21/2022] Open
Abstract
The prevalence of obesity is escalating and has become a worldwide health challenge coinciding with the development of metabolic diseases. Emerging evidence has shown that obesity is accompanied by the infiltration of macrophages into adipose tissue, contributing to a state of low-grade chronic inflammation and dysregulated metabolism. Moreover, in the state of obesity, the phenotype of adipose tissue macrophages switches from the M2 polarized state to the M1 state, thereby contributing to chronic inflammation. Notably, multiple metabolic organs (adipose tissue, gut, skeletal muscle, and the liver) communicate with adipose tissue macrophages via secreting organokines or exosomes. In this review, we systematically summarize how the organokines (adipokines, gut microbiota and its metabolites, gut cytokines, myokines, and hepatokines) and exosomes (adipocyte-, skeletal muscle-, and hepatocyte-derived exosomes) act as important triggers for macrophage recruitment in adipose tissue and adipose tissue macrophage polarization, thus providing further insight into obesity treatment. In addition, we also highlight the complex interaction of organokines with organokines and organokines with exosomes, revealing new paths in understanding adipose tissue macrophage recruitment and polarization.
Collapse
Affiliation(s)
| | | | | | | | | | - Xin-Hua Xiao
- The First Affiliated Hospital, Department of Metabolism and Endocrinology, Hengyang Medical School, University of South China, Hengyang, China
| |
Collapse
|
|
34
|
Choi KJ, Lee JH, Park SB, Na YJ, Jung WH, Lee H, Kim KY. Development of in vitro three-dimensional drug screening system for obesity-related metabolic syndrome. J Pharmacol Sci 2022; 148:377-386. [DOI: 10.1016/j.jphs.2022.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 02/07/2022] [Accepted: 02/09/2022] [Indexed: 10/19/2022] Open
|
|
35
|
Altun I, Yan X, Ussar S. Immune Cell Regulation of White Adipose Progenitor Cell Fate. Front Endocrinol (Lausanne) 2022; 13:859044. [PMID: 35422761 PMCID: PMC9001836 DOI: 10.3389/fendo.2022.859044] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 02/28/2022] [Indexed: 02/03/2023] Open
Abstract
Adipose tissue is essential for energy storage and endocrine regulation of metabolism. Imbalance in energy intake and expenditure result in obesity causing adipose tissue dysfunction. This alters cellular composition of the stromal cell populations and their function. Moreover, the individual cellular composition of each adipose tissue depot, regulated by environmental factors and genetics, determines the ability of the depots to expand and maintain its endocrine and storage function. Thus, stromal cells modulate adipocyte function and vice versa. In this mini-review we discuss heterogeneity in terms of composition and fate of adipose progenitor subtypes and their interactions with and regulation by different immune cell populations. Immune cells are the most diverse cell populations in adipose tissue and play essential roles in regulating adipose tissue function via interaction with adipocytes but also with adipocyte progenitors. We specifically discuss the role of macrophages, mast cells, innate lymphoid cells and T cells in the regulation of adipocyte progenitor proliferation, differentiation and lineage commitment. Understanding the factors and cellular interactions regulating preadipocyte expansion and fate decision will allow the identification of novel mechanisms and therapeutic strategies to promote healthy adipose tissue expansion without systemic metabolic impairment.
Collapse
Affiliation(s)
- Irem Altun
- Research Group Adipocytes and Metabolism, Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Xiaocheng Yan
- Research Group Adipocytes and Metabolism, Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Siegfried Ussar
- Research Group Adipocytes and Metabolism, Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Medicine, Technische Universität München, Munich, Germany
- *Correspondence: Siegfried Ussar,
| |
Collapse
|
|
36
|
Alamri HS, Akiel MA, Alghassab TS, Alfhili MA, Alrfaei BM, Aljumaa M, Barhoumi T. Erythritol modulates the polarization of macrophages: Potential role of tumor necrosis factor-α and Akt pathway. J Food Biochem 2021; 46:e13960. [PMID: 34923647 DOI: 10.1111/jfbc.13960] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 09/15/2021] [Accepted: 09/16/2021] [Indexed: 11/29/2022]
Abstract
Low-calorie sweeteners are substitutes for sugar and frequently used by patients with cardiometabolic diseases. Erythritol, a natural low-calorie sugar alcohol, was linked to cardiometabolic diseases in several recent metabolomics studies. However, the characterization of its role in disease development is lacking. Macrophage polarization orchestrates the immune response in various inflammatory conditions, most notably cardiometabolic disease. Therefore, the physiological effects of Erythritol on THP-1 macrophages were investigated. We observed an increased cellular abundance of proinflammatory M1 macrophages, characterized by CD11c, TNF-α, CD64, CD38, and HLA-DR markers and decreased anti-inflammatory M2 macrophages, characterized by mannose receptor CD206. The, Erythritol increased ROS generation, and the activation of the AKT pathway, cytosolic calcium overload, and cell cycle arrest at the G1 phase. Concomitantly, an increased population of necroptotic macrophages was observed. In conclusion, we provide evidence that Erythritol induced the proinflammatory phenotype in THP-1 macrophages and this was associated with an increased population of necroptotic macrophages. PRACTICAL APPLICATIONS: This assessment provides evidence of the effects of Erythritol on macrophages, particularly THP-1-derived macrophages. Our results support the role of Erythritol in driving the inflammation that is associated with cardiometabolic diseases and provide insights in the role of Erythritol as an inducer of necroptosis in THP-1 derived macrophages that could be associated the disease.
Collapse
Affiliation(s)
- Hassan S Alamri
- Department of Clinical Laboratory Sciences, Collage of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia.,King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia
| | - Maaged A Akiel
- Department of Clinical Laboratory Sciences, Collage of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia.,King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia.,Department of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Talal S Alghassab
- Department of Clinical Laboratory Sciences, Collage of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia.,King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia
| | - Mohammad A Alfhili
- Chair of Medical and Molecular Genetics Research, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Bahauddeen M Alrfaei
- Stem Cell and Regenerative Medicine, King Abdullah International Medical Research Centre (KAIMRC)/King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Maha Aljumaa
- Medical Core Facility and Research Platforms, King Abdullah International Medical Research Centre (KAIMRC), King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia
| | - Tlili Barhoumi
- Medical Core Facility and Research Platforms, King Abdullah International Medical Research Centre (KAIMRC), King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia
| |
Collapse
|
|
37
|
Zhong H, Wang J, Abdullah, Hafeez MA, Guan R, Feng F. Lactobacillus plantarum ZJUFB2 Prevents High Fat Diet-Induced Insulin Resistance in Association With Modulation of the Gut Microbiota. Front Nutr 2021; 8:754222. [PMID: 34805244 PMCID: PMC8604096 DOI: 10.3389/fnut.2021.754222] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 09/14/2021] [Indexed: 12/12/2022] Open
Abstract
Lactobacillus plantarum ZJUFB2 is a novel probiotic isolate derived from Chinese traditional sourdough that possesses promising probiotics properties. This study aimed to investigate the effects of L. plantarum ZJUFB2 (B2) on insulin sensitivity using mice fed on a high-fat diet (HFD) as well as to explore the involved mechanisms. Purposely, male C57BL/6 mice continuously received an intervention of B2 (~109 CFU/day) for 16 weeks. The results showed that B2 treatment remarkably ameliorated insulin resistance and hyperglycemia in HFD-fed mice. The B2 intervention significantly decreased the hepatic lipid accumulation, serum low-density lipoproteins cholesterol, and lipopolysaccharides, and regulated the bile acids levels as well as liver mRNA expression involved in lipid metabolism. Moreover, the B2 intervention significantly changed the gut microbiota, specifically, showed a lower abundance of obesity-related and inflammation-associated microbes, e.g., Ruminococcus and Mogibacteriaceae. Furthermore, it exhibited a higher abundance of short-chain fatty acids and bile salt hydrolas-producing bacteria, such as Bifidobacterium and F16 compared with the HFD group. The findings of this study suggested that B2 is a novel probiotic, effective in preventing insulin resistance by improving the gut microbiota and bile acids.
Collapse
Affiliation(s)
- Hao Zhong
- College of Food Science and Technology, Zhejiang University of Technology, Hangzhou, China
| | - Jian Wang
- College of Food Science and Technology, Zhejiang University of Technology, Hangzhou, China
| | - Abdullah
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou, China
| | - Muhammad Adnan Hafeez
- National Institute of Food Science and Technology, University of Agriculture, Faisalabad, Pakistan
| | - Rongfa Guan
- College of Food Science and Technology, Zhejiang University of Technology, Hangzhou, China
| | - Fengqin Feng
- College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, China
| |
Collapse
|
|
38
|
Correlations between Salivary Immuno-Biochemical Markers and HbA1c in Type 2 Diabetes Subjects before and after Dental Extraction. Antioxidants (Basel) 2021; 10:antiox10111741. [PMID: 34829612 PMCID: PMC8615044 DOI: 10.3390/antiox10111741] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 10/02/2021] [Accepted: 10/28/2021] [Indexed: 12/20/2022] Open
Abstract
Dental extraction can trigger certain sequences of complex processes that involve both hard (alveolar bone) and soft tissue (periodontal ligament, gingiva) remodeling. Type 2 diabetes is a serious risk factor for many oral pathologies, both in terms of progression and severity, but also regarding subsequent rehabilitation possibilities. The aim of this study was to establish whether certain molecules: osteoprotegerin (OPG), kappa B nuclear factor receptor activator ligand (RANKL), hepatocyte growth factor (HGF), tumor necrosis factor-α (TNF-α), interleukin 18 (IL-18), matrix metalloproteinase 9 (MMP-9) and oxidative stress markers-total oxidant status (TOS), total antioxidant capacity (TAC)-evaluated in saliva are modified post-extraction in type 2 diabetes mellitus subjects and whether there is a correlation with HbA1c levels. The aforementioned markers plus HbA1c were investigated in a group of systemically healthy subjects (n = 45) and in a type 2 diabetes mellitus group (n = 41) before and three months after a tooth extraction. Diabetes patients' recorded increased levels of OPG, RANKL, TNF-α, MMP-9, IL-18 and TOS compared to controls both pre- and post-extraction. In both study groups, the average OPG, HGF and TAC level recorded an upward trend three months post-extraction. TNF-α registered a statistically significant decrease only in the diabetes group after dental extraction, together with a decrement of mean HbA1c levels in the diabetes group. By plotting the ROC (receiver operating characteristic) curve, at baseline RANKL, TNF-α, IL-18, MMP-9, TOS and OPG were good predictors of HbA1c levels. Post-extraction, there was a significant correlation between HbA1c and oxidative status biomarkers, however the linear regression model indicated the influence of all studied salivary markers in HbA1c determinism, in a considerable proportion. In conclusion, our study demonstrated that several oxidative status markers and proinflammatory biomarkers are modified in the saliva of diabetic patients and they correlate to HbA1c levels, thus being potential indicators of the post-extraction healing status in the oral cavity.
Collapse
|
|
39
|
Li W, Zeng H, Xu M, Huang C, Tao L, Li J, Zhang T, Chen H, Xia J, Li C, Li X. Oleanolic Acid Improves Obesity-Related Inflammation and Insulin Resistance by Regulating Macrophages Activation. Front Pharmacol 2021; 12:697483. [PMID: 34393781 PMCID: PMC8361479 DOI: 10.3389/fphar.2021.697483] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 06/28/2021] [Indexed: 12/21/2022] Open
Abstract
The chronic low-grade inflammation of adipose tissues, primarily mediated by adipose tissue macrophages (ATMs), is the key pathogenic link between obesity and metabolic disorders. Oleanolic acid (OA) is a natural triterpenoid possessing anti-diabetic and anti-inflammation effects, but the machinery is poorly understood. This study investigated the detailed mechanisms of OA on adipose tissue inflammation in obese mice. C57BL/6J mice were fed with high-fat diet (HFD) for 12 weeks, then daily intragastric administrated with vehicle, 25 and 50 mg/kg OA for 4 weeks. Comparing with vehicle, OA administration in obese mice greatly improved insulin resistance, and reduced adipose tissue hypertrophy, ATM infiltration as well as the M1/M2 ratio. The pro-inflammatory markers were significantly down-regulated by OA in both adipose tissue of obese mice and RAW264.7 macrophages treated with interferon gamma/lipopolysaccharide (IFN-γ/LPS). Furthermore, it was found that OA suppressed activation of mitogen-activated protein kinase (MAPK) signaling and NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome through decreasing voltage dependent anion channels (VDAC) expression and reactive oxygen species (ROS) production. This is the first report that oleanolic acid exerts its benefits by affecting mitochondrial function and macrophage activation.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | | | - Chunli Li
- Institute of Life Sciences, Chongqing Medical University, Chongqing, China
| | - Xi Li
- Institute of Life Sciences, Chongqing Medical University, Chongqing, China
| |
Collapse
|
|
40
|
Nagashimada M, Honda M. Effect of Microbiome on Non-Alcoholic Fatty Liver Disease and the Role of Probiotics, Prebiotics, and Biogenics. Int J Mol Sci 2021; 22:ijms22158008. [PMID: 34360773 PMCID: PMC8348401 DOI: 10.3390/ijms22158008] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 07/21/2021] [Accepted: 07/22/2021] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a leading cause of liver cirrhosis and hepatocellular carcinoma. NAFLD is associated with metabolic disorders such as obesity, insulin resistance, dyslipidemia, steatohepatitis, and liver fibrosis. Liver-resident (Kupffer cells) and recruited macrophages contribute to low-grade chronic inflammation in various tissues by modulating macrophage polarization, which is implicated in the pathogenesis of metabolic diseases. Abnormalities in the intestinal environment, such as the gut microbiota, metabolites, and immune system, are also involved in the pathogenesis and development of NAFLD. Hepatic macrophage activation is induced by the permeation of antigens, endotoxins, and other proinflammatory substances into the bloodstream as a result of increased intestinal permeability. Therefore, it is important to understand the role of the gut–liver axis in influencing macrophage activity, which is central to the pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH). Not only probiotics but also biogenics (heat-killed lactic acid bacteria) are effective in ameliorating the progression of NASH. Here we review the effect of hepatic macrophages/Kupffer cells, other immune cells, intestinal permeability, and immunity on NAFLD and NASH and the impact of probiotics, prebiotics, and biogenesis on those diseases.
Collapse
|
|
41
|
Kolliniati O, Ieronymaki E, Vergadi E, Tsatsanis C. Metabolic Regulation of Macrophage Activation. J Innate Immun 2021; 14:51-68. [PMID: 34247159 DOI: 10.1159/000516780] [Citation(s) in RCA: 82] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 04/19/2021] [Indexed: 11/19/2022] Open
Abstract
Macrophages, the central mediators of innate immune responses, being in the first-line of defense, they have to readily respond to pathogenic or tissue damage signals to initiate the inflammatory cascade. Such rapid responses require energy to support orchestrated production of pro-inflammatory mediators and activation of phagocytosis. Being a cell type that is present in diverse environments and conditions, macrophages have to adapt to different nutritional resources. Thus, macrophages have developed plasticity and are capable of utilizing energy at both normoxic and hypoxic conditions and in the presence of varying concentrations of glucose or other nutrients. Such adaptation is reflected on changes in signaling pathways that modulate responses, accounting for the different activation phenotypes observed. Macrophage metabolism has been tightly associated with distinct activation phenotypes within the range of M1-like and M2-like types. In the context of diseases, systemic changes also affect macrophage metabolism, as in diabetes and insulin resistance, which results in altered metabolism and distinct activation phenotypes in the adipose tissue or in the periphery. In the context of solid tumors, tumor-associated macrophages adapt in the hypoxic environment, which results in metabolic changes that are reflected on an activation phenotype that supports tumor growth. Coordination of environmental and pathogenic signals determines macrophage metabolism, which in turn shapes the type and magnitude of the response. Therefore, modulating macrophage metabolism provides a potential therapeutic approach for inflammatory diseases and cancer.
Collapse
Affiliation(s)
- Ourania Kolliniati
- Laboratory of Clinical Chemistry, Medical School, University of Crete, Heraklion, Greece.,Department of Pediatrics, Medical School, University of Crete, Heraklion, Greece.,Institute of Molecular Biology and Biotechnology, FORTH, Heraklion, Greece
| | - Eleftheria Ieronymaki
- Laboratory of Clinical Chemistry, Medical School, University of Crete, Heraklion, Greece.,Institute of Molecular Biology and Biotechnology, FORTH, Heraklion, Greece
| | - Eleni Vergadi
- Department of Pediatrics, Medical School, University of Crete, Heraklion, Greece
| | - Christos Tsatsanis
- Laboratory of Clinical Chemistry, Medical School, University of Crete, Heraklion, Greece.,Institute of Molecular Biology and Biotechnology, FORTH, Heraklion, Greece
| |
Collapse
|
|
42
|
On the Role of Paraoxonase-1 and Chemokine Ligand 2 (C-C motif) in Metabolic Alterations Linked to Inflammation and Disease. A 2021 Update. Biomolecules 2021; 11:biom11070971. [PMID: 34356595 PMCID: PMC8301931 DOI: 10.3390/biom11070971] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 06/23/2021] [Accepted: 06/29/2021] [Indexed: 02/08/2023] Open
Abstract
Infectious and many non-infectious diseases share common molecular mechanisms. Among them, oxidative stress and the subsequent inflammatory reaction are of particular note. Metabolic disorders induced by external agents, be they bacterial or viral pathogens, excessive calorie intake, poor-quality nutrients, or environmental factors produce an imbalance between the production of free radicals and endogenous antioxidant systems; the consequence being the oxidation of lipids, proteins, and nucleic acids. Oxidation and inflammation are closely related, and whether oxidative stress and inflammation represent the causes or consequences of cellular pathology, both produce metabolic alterations that influence the pathogenesis of the disease. In this review, we highlight two key molecules in the regulation of these processes: Paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2). PON1 is an enzyme bound to high-density lipoproteins. It breaks down lipid peroxides in lipoproteins and cells, participates in the protection conferred by HDL against different infectious agents, and is considered part of the innate immune system. With PON1 deficiency, CCL2 production increases, inducing migration and infiltration of immune cells in target tissues and disturbing normal metabolic function. This disruption involves pathways controlling cellular homeostasis as well as metabolically-driven chronic inflammatory states. Hence, an understanding of these relationships would help improve treatments and, as well, identify new therapeutic targets.
Collapse
|
|
43
|
Rivera K, Quiñones V, Amigo L, Santander N, Salas-Pérez F, Xavier A, Fernández-Galilea M, Carrasco G, Cabrera D, Arrese M, Busso D, Andia ME, Rigotti A. Lipoprotein receptor SR-B1 deficiency enhances adipose tissue inflammation and reduces susceptibility to hepatic steatosis during diet-induced obesity in mice. Biochim Biophys Acta Mol Cell Biol Lipids 2021; 1866:158909. [PMID: 33631309 DOI: 10.1016/j.bbalip.2021.158909] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 02/05/2021] [Accepted: 02/17/2021] [Indexed: 12/31/2022]
Abstract
Scavenger receptor class B type 1 (SR-B1) is a membrane lipoprotein receptor/lipid transporter involved in the pathogenesis of atherosclerosis, but its role in obesity and fatty liver development is unclear. Here, we determined the effects of SR-B1 deficiency on plasma metabolic and inflammatory parameters as well as fat deposition in adipose tissue and liver during obesity. To induce obesity, we performed high-fat diet (HFD) exposure for 12 weeks in male SR-B1 knock-out (SR-B1-/-, n = 14) and wild-type (WT, n = 12) mice. Compared to HFD-fed WT mice, plasma from HFD-fed SR-B1-/- animals exhibited increased total cholesterol, triglycerides (TG) and tumor necrosis factor-α (TNF-α) levels. In addition, hypertrophied adipocytes and macrophage-containing crown-like structures (CLS) were observed in adipose tissue from HFD-fed SR-B1 deficient mice. Remarkably, liver from obese SR-B1-/- mice showed attenuated TG content, dysregulation in hepatic peroxisome proliferator-activated receptors (PPARs) expression, increased hepatic TG secretion, and altered hepatic fatty acid (FA) composition. In conclusion, we show that SR-B1 deficiency alters the metabolic environment of obese mice through modulation of liver and adipose tissue lipid accumulation. Our findings provide the basis for further elucidation of SR-B1's role in obesity and fatty liver, two major public health issues that increase the risk of advanced chronic diseases and overall mortality.
Collapse
Affiliation(s)
- Katherine Rivera
- Department of Nutrition, Diabetes, and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile; Millennium Nucleus for Cardiovascular Magnetic Resonance, Santiago 7820436, Chile.
| | - Verónica Quiñones
- Department of Nutrition, Diabetes, and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile.
| | - Ludwig Amigo
- Department of Nutrition, Diabetes, and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile.
| | - Nicolás Santander
- Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA.
| | - Francisca Salas-Pérez
- Instituto de Ciencias de la Salud, Universidad de O'Higgins, Rancagua 2820000, Chile.
| | - Aline Xavier
- Millennium Nucleus for Cardiovascular Magnetic Resonance, Santiago 7820436, Chile; Biomedical Imaging Center, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 7820436, Chile.
| | - Marta Fernández-Galilea
- Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, Pamplona 31008, Spain; IDISNA, Navarra's Health Research Institute, Pamplona 31008, Spain.
| | - Gonzalo Carrasco
- Department of Pathology, Hospital Clínico Universidad de Chile, Santiago 8320000, Chile.
| | - Daniel Cabrera
- Department of Gastroenterology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile; Faculty of Medical Sciences, School of Medicine, Universidad Bernardo O Higgins, Santiago 8370854, Chile.
| | - Marco Arrese
- Department of Gastroenterology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile; Centro de Envejecimiento y Regeneración (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
| | - Dolores Busso
- Biomedical Research and Innovation Center, Faculty of Medicine, Universidad de los Andes, Santiago 111711, Chile.
| | - Marcelo E Andia
- Millennium Nucleus for Cardiovascular Magnetic Resonance, Santiago 7820436, Chile; Biomedical Imaging Center, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 7820436, Chile.
| | - Attilio Rigotti
- Department of Nutrition, Diabetes, and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile; Millennium Nucleus for Cardiovascular Magnetic Resonance, Santiago 7820436, Chile; Center of Molecular Nutrition and Chronic Diseases, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile.
| |
Collapse
|
|
44
|
Ramadhin J, Silva-Moraes V, Nagy T, Norberg T, Harn D. A Comparison of Two Structurally Related Human Milk Oligosaccharide Conjugates in a Model of Diet-Induced Obesity. Front Immunol 2021; 12:668217. [PMID: 34093565 PMCID: PMC8173488 DOI: 10.3389/fimmu.2021.668217] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 04/30/2021] [Indexed: 12/29/2022] Open
Abstract
Obesity is the largest risk factor for the development of chronic diseases in industrialized countries. Excessive fat accumulation triggers a state of chronic low-grade inflammation to the detriment of numerous organs. To address this problem, our lab has been examining the anti-inflammatory mechanisms of two human milk oligosaccharides (HMOs), lacto-N-fucopentaose III (LNFPIII) and lacto-N-neotetraose (LNnT). LNFPIII and LNnT are HMOs that differ in structure via presence/absence of an α1,3-linked fucose. We utilize LNFPIII and LNnT in conjugate form, where 10-12 molecules of LNFPIII or LNnT are conjugated to a 40 kDa dextran carrier (P3DEX/NTDEX). Previous studies from our lab have shown that LNFPIII conjugates are anti-inflammatory, act on multiple cell types, and are therapeutic in a wide range of murine inflammatory disease models. The α1,3-linked fucose residue on LNFPIII makes it difficult and more expensive to synthesize. Therefore, we asked if LNnT conjugates induced similar therapeutic effects to LNFPIII. Herein, we compare the therapeutic effects of P3DEX and NTDEX in a model of diet-induced obesity (DIO). Male C57BL/6 mice were placed on a high-fat diet for six weeks and then injected twice per week for eight weeks with 25µg of 40 kDa dextran (DEX; vehicle control), P3DEX, or NTDEX. We found that treatment with P3DEX, but not NTDEX, led to reductions in body weight, adipose tissue (AT) weights, and fasting blood glucose levels. Mice treated with P3DEX also demonstrated improvements in glucose homeostasis and insulin tolerance. Treatment with P3DEX or NTDEX also induced different profiles of serum chemokines, cytokines, adipokines, and incretin hormones, with P3DEX notably reducing circulating levels of leptin and resistin. P3DEX also reduced WAT inflammation and hepatic lipid accumulation, whereas NTDEX seemed to worsen these parameters. These results suggest that the small structural difference between P3DEX and NTDEX has significant effects on the conjugates' therapeutic abilities. Future work will focus on identifying the receptors for these conjugates and delineating the mechanisms by which P3DEX and NTDEX exert their effects.
Collapse
Affiliation(s)
- Jessica Ramadhin
- Department of Infectious Diseases, University of Georgia, Athens, GA, United States
| | - Vanessa Silva-Moraes
- Department of Infectious Diseases, University of Georgia, Athens, GA, United States
| | - Tamas Nagy
- Department of Pathology, University of Georgia, Athens, GA, United States
| | - Thomas Norberg
- Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden
| | - Donald Harn
- Department of Infectious Diseases, University of Georgia, Athens, GA, United States
| |
Collapse
|
|
45
|
Turner L, Santosa S. Putting ATM to BED: How Adipose Tissue Macrophages Are Affected by Bariatric Surgery, Exercise, and Dietary Fatty Acids. Adv Nutr 2021; 12:1893-1910. [PMID: 33979430 PMCID: PMC8483961 DOI: 10.1093/advances/nmab011] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 12/17/2020] [Accepted: 01/19/2021] [Indexed: 12/20/2022] Open
Abstract
With increasing adiposity in obesity, adipose tissue macrophages contribute to adipose tissue malfunction and increased circulating proinflammatory cytokines. The chronic low-grade inflammation that occurs in obesity ultimately gives rise to a state of metainflammation that increases the risk of metabolic disease. To date, only lifestyle and surgical interventions have been shown to be somewhat effective at reversing the negative consequences of obesity and restoring adipose tissue homeostasis. Exercise, dietary interventions, and bariatric surgery result in immunomodulation, and for some individuals their effects are significant with or without weight loss. Robust evidence suggests that these interventions reduce chronic inflammation, in part, by affecting macrophage infiltration and promoting a phenotypic switch from the M1- to M2-like macrophages. The purpose of this review is to discuss the impact of dietary fatty acids, exercise, and bariatric surgery on cellular characteristics affecting adipose tissue macrophage presence and phenotypes in obesity.
Collapse
Affiliation(s)
- Laurent Turner
- Department of Health, Kinesiology, and Applied Physiology, Concordia University, Montreal, Quebec, Canada,Metabolism, Obesity, and Nutrition Lab, PERFORM Centre, Concordia University, Montreal, Quebec, Canada
| | | |
Collapse
|
|
46
|
Singanayagam A, Triantafyllou E. Macrophages in Chronic Liver Failure: Diversity, Plasticity and Therapeutic Targeting. Front Immunol 2021; 12:661182. [PMID: 33868313 PMCID: PMC8051585 DOI: 10.3389/fimmu.2021.661182] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Accepted: 03/18/2021] [Indexed: 12/12/2022] Open
Abstract
Chronic liver injury results in immune-driven progressive fibrosis, with risk of cirrhosis development and impact on morbidity and mortality. Persistent liver cell damage and death causes immune cell activation and inflammation. Patients with advanced cirrhosis additionally experience pathological bacterial translocation, exposure to microbial products and chronic engagement of the immune system. Bacterial infections have a high incidence in cirrhosis, with spontaneous bacterial peritonitis being the most common, while the subsequent systemic inflammation, organ failure and immune dysregulation increase the mortality risk. Tissue-resident and recruited macrophages play a central part in the development of inflammation and fibrosis progression. In the liver, adipose tissue, peritoneum and intestines, diverse macrophage populations exhibit great phenotypic and functional plasticity determined by their ontogeny, epigenetic programming and local microenvironment. These changes can, at different times, promote or ameliorate disease states and therefore represent potential targets for macrophage-directed therapies. In this review, we discuss the evidence for macrophage phenotypic and functional alterations in tissue compartments during the development and progression of chronic liver failure in different aetiologies and highlight the potential of macrophage modulation as a therapeutic strategy for liver disease.
Collapse
Affiliation(s)
- Arjuna Singanayagam
- Infection and Immunity Clinical Academic Group, St. George’s University Hospitals NHS Foundation Trust, London, United Kingdom
| | - Evangelos Triantafyllou
- Section of Hepatology and Gastroenterology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom
| |
Collapse
|
|
47
|
Ni Y, Ni L, Ma L, Wang Z, Zhao Y, Hu L, Zheng L, Fu Z. Neuroprotective effects of ProBeptigen/CMI-168 on aging-induced cognitive decline and neuroinflammation in mice: a comparison with essence of chicken. Acta Biochim Biophys Sin (Shanghai) 2021; 53:419-429. [PMID: 33637986 DOI: 10.1093/abbs/gmab009] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Indexed: 12/31/2022] Open
Abstract
Neuroinflammation and cognitive decline are the key pathological features in aging that bring detrimental impacts upon quality of life. However, there is no effective anti-aging pharmacological therapy thus far. Dietary supplements in particular essence of chicken (EC) has been found to be an effective remedy for alleviating mental stress and improving memory. In addition, a novel hydrolyzed chicken extract, ProBeptigen/CMI-168 (PB), showed beneficial effects on cognitive ability. However, the antiaging effect and possible mechanism of PB and EC are still unknown. Here, we investigated the antiaging effects of PB and EC on hippocampus-related cognitive decline and neuroinflammation in aged mice. PB and EC were administered for 16 weeks in 10-month-old mice. Both PB and EC treatments ameliorated age-related deterioration of learning and memory, and attenuated oxidative stress and inflammation in the hippocampus. These results were associated with decreased inflammatory cytokine levels and increased neurotransmitter levels in the hippocampus. The overall effects of improving aging-induced cognitive decline were more robust in PB-treated mice, while EC was effective in decreasing oxidative stress and inflammation. Moreover, alterations in the diversity and composition of the gut microbiota in aged mice were also regulated by both PB and EC, which induced distinguished features in the gut microbiota and their related functions. This study showed that PB exerts neuroprotective effects in aged mice, the mechanism of which might be different from that of EC. Therefore, PB has a potential as dietary supplement for ameliorating cognitive dysfunction and neuroinflammation in elderly individuals.
Collapse
Affiliation(s)
- Yinhua Ni
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Liyang Ni
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Lingyan Ma
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Zhe Wang
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Yufeng Zhao
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Luting Hu
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Liujie Zheng
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Zhengwei Fu
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| |
Collapse
|
|
48
|
Teng LL, Mu RF, Liu YC, Xiao CJ, Li DS, Gao JX, Guo K, Li XN, Liu Y, Zeng F, Li SH. Immunosuppressive and Adipogenesis Inhibitory Sesterterpenoids with a Macrocyclic Ether System from Eurysolen gracilis. Org Lett 2021; 23:2232-2237. [PMID: 33667109 DOI: 10.1021/acs.orglett.1c00369] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Lin-Lin Teng
- State Key Laboratory of Phytochemistry and Plant Resources in West China, and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, P. R. China
- University of Chinese Academy of Sciences, Beijing 100049, P. R. China
| | - Rong-Fang Mu
- State Key Laboratory of Phytochemistry and Plant Resources in West China, and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, P. R. China
- University of Chinese Academy of Sciences, Beijing 100049, P. R. China
| | - Yan-Chun Liu
- State Key Laboratory of Phytochemistry and Plant Resources in West China, and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, P. R. China
| | - Chao-Jiang Xiao
- State Key Laboratory of Phytochemistry and Plant Resources in West China, and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, P. R. China
- Institute of Materia Medica & College of Pharmacy, Dali University, Dali 671000, P. R. China
| | - De-Sen Li
- State Key Laboratory of Phytochemistry and Plant Resources in West China, and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, P. R. China
- University of Chinese Academy of Sciences, Beijing 100049, P. R. China
| | - Jian-Xiong Gao
- State Key Laboratory of Phytochemistry and Plant Resources in West China, and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, P. R. China
- University of Chinese Academy of Sciences, Beijing 100049, P. R. China
| | - Kai Guo
- State Key Laboratory of Southwestern Chinese Medicine Resources, and Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P. R. China
| | - Xiao-Nian Li
- State Key Laboratory of Phytochemistry and Plant Resources in West China, and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, P. R. China
| | - Yan Liu
- State Key Laboratory of Phytochemistry and Plant Resources in West China, and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, P. R. China
| | - Fang Zeng
- Acupuncture & Tuina School, The 3rd Teaching Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P. R. China
| | - Sheng-Hong Li
- State Key Laboratory of Phytochemistry and Plant Resources in West China, and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, P. R. China
- State Key Laboratory of Southwestern Chinese Medicine Resources, and Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P. R. China
| |
Collapse
|
|
49
|
Lu RJ, Wang EK, Benayoun BA. Functional genomics of inflamm-aging and immunosenescence. Brief Funct Genomics 2021; 21:43-55. [PMID: 33690792 DOI: 10.1093/bfgp/elab009] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Revised: 01/26/2021] [Accepted: 01/29/2021] [Indexed: 02/07/2023] Open
Abstract
The aging population is at a higher risk for age-related diseases and infections. This observation could be due to immunosenescence: the decline in immune efficacy of both the innate and the adaptive immune systems. Age-related immune decline also links to the concept of 'inflamm-aging,' whereby aging is accompanied by sterile chronic inflammation. Along with a decline in immune function, aging is accompanied by a widespread of 'omics' remodeling. Transcriptional landscape changes linked to key pathways of immune function have been identified across studies, such as macrophages having decreased expression of genes associated to phagocytosis, a major function of macrophages. Therefore, a key mechanism underlying innate immune cell dysfunction during aging may stem from dysregulation of youthful genomic networks. In this review, we discuss both molecular and cellular phenotypes of innate immune cells that contribute to age-related inflammation.
Collapse
Affiliation(s)
- Ryan J Lu
- Leonard Davis School of Gerontology at the University of Southern California
| | - Emily K Wang
- Leonard Davis School of Gerontology at the University of Southern California
| | - Bérénice A Benayoun
- Leonard Davis School of Gerontology at the University of Southern California
| |
Collapse
|
|
50
|
Navy Bean Supplementation in Established High-Fat Diet-Induced Obesity Attenuates the Severity of the Obese Inflammatory Phenotype. Nutrients 2021; 13:nu13030757. [PMID: 33652785 PMCID: PMC7996849 DOI: 10.3390/nu13030757] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 02/05/2021] [Accepted: 02/19/2021] [Indexed: 02/06/2023] Open
Abstract
Cooked common beans (Phaseolus vulgaris) improve intestinal health in lean mice and attenuate intestinal dysbiosis and inflammation when consumed concurrent with obesity development. We determined the effects of a high-fat (HF) bean supplemented diet in mice with established obesity (induced by 12 weeks of HF diet (60% fat as kcal)) compared to obese mice consuming a HF or low-fat (LF) weight loss control diet. Obese C57BL/6 male mice remained consuming HF for eight weeks or were randomly switched from HF to an isocaloric HF with 15.7% cooked navy bean powder diet (HF→HFB) or LF (11% fat as kcal; HF→LF) (n = 12/group). HF→HFB improved the obese phenotype, including (i) fecal microbiome (increased Prevotella, Akkermansia muciniphila, and short-chain fatty acid levels), (ii) intestinal health (increased ZO-1, claudin-2, Muc2, Relmβ, and Reg3γ expression), and (iii) reduced adipose tissue (AT) inflammatory proteins (NFκBp65, STAT3, IL-6, MCP-1, and MIP-1α), versus HF (p < 0.05). Conversely, HF→LF reduced body weight and circulating hormones (leptin, resistin, and PAI-1) versus HF and HF→HFB (p < 0.05); however, AT inflammation and intestinal health markers were not improved to the same degree as HF→HFB (p < 0.05). Despite remaining on a HF obesogenic diet, introducing beans in established obesity improved the obese phenotype (intestinal health and adipose inflammation) more substantially than weight loss alone.
Collapse
|