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Wang S, Sun W, Cheng Y, Wang L, Ma S, Jing F, Zhang X, Zhou X. Relationship between plasma 12,13-diHOME level and nonalcoholic fatty liver disease in patients with type 2 diabetes and obesity. Minerva Endocrinol (Torino) 2025; 50:72-83. [PMID: 33855386 DOI: 10.23736/s2724-6507.21.03424-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) was one of the newly found lipokines. The goal of this study was to investigate whether the 12,13-diHOME was associated with related metabolic markers of nonalcoholic fatty liver disease (NAFLD) in a Chinese population with type 2 diabetes (T2DM) and obesity. METHODS This cross-sectional study enrolled 202 subjects with T2DM. Anthropometric parameters, 12,13-diHOME, serum lipids levels, fasting blood-glucose (FBG), serum glycosylated hemoglobin (HbA1c), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), liver and kidney function parameters were collected. NAFLD was diagnosed based on abdominal ultrasonography examination results. A computer-aided ultrasound quantitative method was applied to evaluate the liver fat content (LFC). RESULTS The number of the patients with fatty liver was 139 (68.81%) and those with non-fatty liver was 63 (31.19%). Subjects with NAFLD had a higher body mass index (BMI), diastolic blood pressure, serum alanine aminotransferase (ALT), triglyceride (TG), HOMA-IR, LFC, P<0.05 for all. But no significant difference was found in plasma 12,13-diHOME level (P=0.967), though its level trend was higher in non-NAFLD group. Plasma 12,13-diHOME was positively correlated with aspartate aminotransferase (AST), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), blood urea nitrogen (BUN), free fatty acid (FFA), C-peptide, FINS and HOMA-IR. It was negatively correlated with height, body weight, glomerular filtration rate (eGFR) and HbA1c. CONCLUSIONS Although 12,13-diHOME was correlated with AST, TC, HDL-C, BUN, FFA, C-peptide, FINS, HOMA-IR, eGFR and HbA1c, there was no significant difference in 12,13-diHOME level between the two groups. However, more research should be carried on about this newly-found lipokine.
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Affiliation(s)
- Sichao Wang
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China
| | - Weixia Sun
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Yiping Cheng
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Lei Wang
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Shizhan Ma
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Fei Jing
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Xiujuan Zhang
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Xinli Zhou
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China -
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Zhang L, El-Shabrawi M, Baur LA, Byrne CD, Targher G, Kehar M, Porta G, Lee WS, Lefere S, Turan S, Alisi A, Weiss R, Faienza MF, Ashraf A, Sundaram SS, Srivastava A, De Bruyne R, Kang Y, Bacopoulou F, Zhou YH, Darma A, Lupsor-Platon M, Hamaguchi M, Misra A, Méndez-Sánchez N, Ng NBH, Marcus C, Staiano AE, Waheed N, Alqahtani SA, Giannini C, Ocama P, Nguyen MH, Arias-Loste MT, Ahmed MR, Sebastiani G, Poovorawan Y, Al Mahtab M, Pericàs JM, Reverbel da Silveira T, Hegyi P, Azaz A, Isa HM, Lertudomphonwanit C, Farrag MI, Nugud AAA, Du HW, Qi KM, Mouane N, Cheng XR, Al Lawati T, Fagundes EDT, Ghazinyan H, Hadjipanayis A, Fan JG, Gimiga N, Kamal NM, Ștefănescu G, Hong L, Diaconescu S, Li M, George J, Zheng MH. An international multidisciplinary consensus on pediatric metabolic dysfunction-associated fatty liver disease. MED 2024; 5:797-815.e2. [PMID: 38677287 DOI: 10.1016/j.medj.2024.03.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 02/20/2024] [Accepted: 03/26/2024] [Indexed: 04/29/2024]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in children and adolescents, particularly those with obesity. NAFLD is considered a hepatic manifestation of the metabolic syndrome due to its close associations with abdominal obesity, insulin resistance, and atherogenic dyslipidemia. Experts have proposed an alternative terminology, metabolic dysfunction-associated fatty liver disease (MAFLD), to better reflect its pathophysiology. This study aimed to develop consensus statements and recommendations for pediatric MAFLD through collaboration among international experts. METHODS A group of 65 experts from 35 countries and six continents, including pediatricians, hepatologists, and endocrinologists, participated in a consensus development process. The process encompassed various aspects of pediatric MAFLD, including epidemiology, mechanisms, screening, and management. FINDINGS In round 1, we received 65 surveys from 35 countries and analyzed these results, which informed us that 73.3% of respondents agreed with 20 draft statements while 23.8% agreed somewhat. The mean percentage of agreement or somewhat agreement increased to 80.85% and 15.75%, respectively, in round 2. The final statements covered a wide range of topics related to epidemiology, pathophysiology, and strategies for screening and managing pediatric MAFLD. CONCLUSIONS The consensus statements and recommendations developed by an international expert panel serve to optimize clinical outcomes and improve the quality of life for children and adolescents with MAFLD. These findings emphasize the need for standardized approaches in diagnosing and treating pediatric MAFLD. FUNDING This work was funded by the National Natural Science Foundation of China (82070588, 82370577), the National Key R&D Program of China (2023YFA1800801), National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014), the Wuxi Taihu Talent Plan (DJTD202106), and the Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021007).
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Affiliation(s)
- Le Zhang
- Department of Paediatrics, Affiliated Children's Hospital of Jiangnan University (Wuxi Children's Hospital), Wuxi, China
| | - Mortada El-Shabrawi
- Department of Pediatrics and Pediatric Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Louise A Baur
- Children's Hospital Westmead Clinical School, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK; National Institute for Health and Care Research Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK
| | - Giovanni Targher
- Department of Medicine, University of Verona, Verona, Italy; Metabolic Diseases Research Unit, IRCCS Sacro Cuore - Don Calabria Hospital, Negrar di Valpolicella, Italy
| | - Mohit Kehar
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Eastern Ontario, Department of Pediatrics, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Gilda Porta
- Pediatric Hepatology, Transplant Unit, Hospital Sírio-Libanês, Hospital Municipal Infantil Menino Jesus, Sau Paulo, Brazil
| | - Way Seah Lee
- Department of Paediatrics, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
| | - Sander Lefere
- Hepatology Research Unit, Department Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; Liver Research Center Ghent, Ghent University, Ghent, Belgium
| | - Serap Turan
- Pediatric Endocrinology and Diabetes, Marmara University School of Medicine, Istanbul, Turkey
| | - Anna Alisi
- Research Unit of Molecular Genetics of Complex Phenotypes, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Ram Weiss
- Department of Pediatrics, Ruth Children's Hospital, Rambam Medical Center and the Bruce Rappaport School of Medicine, Technion, Haifa, Israel
| | - Maria Felicia Faienza
- Pediatric Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari "Aldo Moro", Bari, Italy
| | - Ambika Ashraf
- Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Shikha S Sundaram
- Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Pediatric Liver Center, Children's Hospital Colorado, University of Colorado School of Medicine and Anschutz Medical Campus, Aurora, CO, USA
| | - Anshu Srivastava
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Ruth De Bruyne
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Ghent University Hospital, Ghent, Belgium
| | - Yunkoo Kang
- Department of Pediatrics, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Flora Bacopoulou
- Center for Adolescent Medicine and UNESCO Chair in Adolescent Health Care, Aghia Sophia Children's Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece; University Research Institute of Maternal and Child Health & Precision Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Yong-Hai Zhou
- Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Andy Darma
- Department of Pediatrics, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Monica Lupsor-Platon
- Department of Medical Imaging, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania; "Prof. Dr. O. Fodor" Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania
| | - Masahide Hamaguchi
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | - Anoop Misra
- Fortis-C-DOC Centre of Excellence for Diabetes, Metabolic Diseases and Endocrinology, New Delhi, India; National Diabetes, Obesity and Cholesterol Foundation (N-DOC), New Delhi, India; Diabetes Foundation, New Delhi, India
| | - Nahum Méndez-Sánchez
- Liver Research Unit, Medica Sur Clinic and Foundation and Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
| | - Nicholas Beng Hui Ng
- Department of Paediatrics, Khoo Teck Puat - National University Children's Medical Institute, National University Hospital, Singapore, Singapore; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Claude Marcus
- Department of Clinical Science, Intervention and Technology, Division of Pediatrics, Karolinska Institutet, Stockholm, Sweden
| | | | - Nadia Waheed
- Department of Pediatrics, Shaheed Zulfiqar Ali Bhutto Medical University, Pakistan Institute of Medical Sciences, Islamabad, Pakistan
| | - Saleh A Alqahtani
- Organ Transplantation Center of Excellence, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia; Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA
| | - Cosimo Giannini
- Department of Pediatrics, University of Chieti, Chieti, Italy
| | - Ponsiano Ocama
- Department of Internal Medicine, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA; Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA
| | - Maria Teresa Arias-Loste
- Hospital Universitario Marqués de Valdecilla, Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Instituto de Investigación Marqués de Valdecilla (IDIVAL), Santander, Spain
| | - Mohamed Rabea Ahmed
- Department of Pediatrics, Jahra Hospital, Kuwait and Department of Pediatrics, National Hepatology and Tropical Medicine Research Institute (NHTMRI), Cairo, Egypt
| | - Giada Sebastiani
- Division of Gastroenterology and Hepatology and Division of Infectious Diseases, McGill University Health Centre, Montreal, QC, Canada
| | - Yong Poovorawan
- Centre of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka, Bangladesh
| | - Juan M Pericàs
- Liver Unit, Vall d'Hebron University Hospital, Vall d'Hebron Institute for Research (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; Centros de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | | | - Peter Hegyi
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary; Center for Translational Medicine, Semmelweis University, Budapest, Hungary; Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Amer Azaz
- Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
| | - Hasan M Isa
- Pediatric Department, Salmaniya Medical Complex and Pediatric Department, Arabian Gulf University, Manama, Bahrain
| | - Chatmanee Lertudomphonwanit
- Division of Gastroenterology, Department of Paediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Mona Issa Farrag
- Department of Pediatrics and Pediatric Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Abd Alwahab Nugud
- Department of Pediatrics and Pediatric Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hong-Wei Du
- Department of Paediatrics, First Hospital of Jilin University, Changchun, China
| | - Ke-Min Qi
- Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Nezha Mouane
- Department of Pediatric Gastroenterology Hepatology and Nutrition, Academic Children's Hospital Ibn Sina, Mohammed V University, Rabat, Morocco
| | - Xin-Ran Cheng
- Department of Paediatric Genetics, Endocrinology and Metabolism, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | | | - Eleonora D T Fagundes
- Department of Pediatrics, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Hasmik Ghazinyan
- Department of Hepatology, Nikomed Medical Center, Yerevan, Armenia
| | | | - Jian-Gao Fan
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai, China
| | - Nicoleta Gimiga
- Clinical Department of Pediatric Gastroenterology, "St. Mary" Emergency Children's Hospital, Iași, Romania; Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, Iași, Romania
| | - Naglaa M Kamal
- Department of Pediatrics and Pediatric Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt; Pediatric Hepatology and Gastroenterology, Alhada Armed Forces Hospital, Taif, Saudi Arabia
| | - Gabriela Ștefănescu
- Department of Gastroenterology, "Grigore T. Popa" University of Medicine and Pharmacy, Iași, Romania
| | - Li Hong
- Department of Clinical Nutrition, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Smaranda Diaconescu
- Medical-Surgical Department, Faculty of Medicine, University "Titu Maiorescu", Bucuresti, Romania
| | - Ming Li
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, University of Sydney, Sydney, NSW, Australia.
| | - Ming-Hua Zheng
- MAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Institute of Hepatology, Wenzhou Medical University, Wenzhou, China; Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China.
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Bornstein MR, Tian R, Arany Z. Human cardiac metabolism. Cell Metab 2024; 36:1456-1481. [PMID: 38959861 PMCID: PMC11290709 DOI: 10.1016/j.cmet.2024.06.003] [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: 01/06/2024] [Revised: 04/12/2024] [Accepted: 06/05/2024] [Indexed: 07/05/2024]
Abstract
The heart is the most metabolically active organ in the human body, and cardiac metabolism has been studied for decades. However, the bulk of studies have focused on animal models. The objective of this review is to summarize specifically what is known about cardiac metabolism in humans. Techniques available to study human cardiac metabolism are first discussed, followed by a review of human cardiac metabolism in health and in heart failure. Mechanistic insights, where available, are reviewed, and the evidence for the contribution of metabolic insufficiency to heart failure, as well as past and current attempts at metabolism-based therapies, is also discussed.
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Affiliation(s)
- Marc R Bornstein
- Cardiovascular Institute Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Rong Tian
- Mitochondria and Metabolism Center, Department of Anesthesiology & Pain Medicine, University of Washington, Seattle, WA, USA
| | - Zoltan Arany
- Cardiovascular Institute Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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Li Z, Gong R, Chu H, Zeng J, Chen C, Xu S, Hu L, Gao W, Zhang L, Yuan H, Cheng Z, Wang C, Du M, Zhu Q, Zhang L, Rong L, Hu X, Yang L. A universal plasma metabolites-derived signature predicts cardiovascular disease risk in MAFLD. Atherosclerosis 2024; 392:117526. [PMID: 38581738 DOI: 10.1016/j.atherosclerosis.2024.117526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 03/19/2024] [Accepted: 03/21/2024] [Indexed: 04/08/2024]
Abstract
BACKGROUND Metabolic associated fatty liver disease (MAFLD) is a novel concept proposed in 2020, which is more practical for identifying patients with fatty liver disease with high risk of disease progression. Fatty liver is a driver for extrahepatic complications, particularly cardiovascular diseases (CVD). Although the risk of CVD in MAFLD could be predicted by carotid ultrasound test, a very early stage prediction method before the formation of pathological damage is still lacking. METHODS Stool microbiomes and plasma metabolites were compared across 196 well-characterized participants encompassing normal controls, simple MAFLD patients, MAFLD patients with carotid artery pathological changes, and MAFLD patients with diagnosed coronary artery disease (CAD). 16S rDNA sequencing data and untargeted metabolomic profiles were interrogatively analyzed using differential abundance analysis and random forest (RF) machine learning algorithm to identify discriminatory gut microbiomes and metabolomic. RESULTS Characteristic microbial changes in MAFLD patients with CVD risk were represented by the increase of Clostridia and Firmicutes-to-Bacteroidetes ratios. Faecalibacterium was negatively correlated with mean-intima-media thickness (IMT), TC, and TG. Megamonas, Bacteroides, Parabacteroides, and Escherichia were positively correlated with the exacerbation of pathological indexes. MAFLD patients with CVD risk were characterized by the decrease of lithocholic acid taurine conjugate, and the increase of ethylvanillin propylene glycol acetal, both of which had close relationship with Ruminococcus and Gemmiger. Biotin l-sulfoxide had positive correlation with mean-IMT, TG, and weight. The general auxin pesticide beta-naphthoxyacetic acid and the food additive glucosyl steviol were both positively correlated with the increase of mean-IMT. The model combining the metabolite signatures with 9 clinical parameters accurately distinguished MAFLD with CVD risk in the proband and validation cohort. It was found that citral was the most important discriminative metabolite marker, which was validated by both in vitro and in vivo experiments. CONCLUSIONS Simple MAFLD patients and MAFLD patients with CVD risk had divergent gut microbes and plasma metabolites. The predictive model based on metabolites and 9 clinical parameters could effectively discriminate MAFLD patients with CVD risk at a very early stage.
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Affiliation(s)
- Zhonglin Li
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China
| | - Rui Gong
- Health Management Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Huikuan Chu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China
| | - Junchao Zeng
- Health Management Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Can Chen
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, China
| | - Sanping Xu
- Health Management Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lilin Hu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China
| | - Wenkang Gao
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China
| | - Li Zhang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China
| | - Hang Yuan
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China
| | - Zilu Cheng
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China
| | - Cheng Wang
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, China
| | - Meng Du
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, China
| | - Qingjing Zhu
- Jinyintan Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; Wuhan Medical Treatment Centre, Wuhan, 430070, China
| | - Li Zhang
- Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China
| | - Lin Rong
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.
| | - Xiaoqing Hu
- Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.
| | - Ling Yang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.
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Colosimo S, Mitra SK, Chaudhury T, Marchesini G. Insulin resistance and metabolic flexibility as drivers of liver and cardiac disease in T2DM. Diabetes Res Clin Pract 2023; 206:111016. [PMID: 37979728 DOI: 10.1016/j.diabres.2023.111016] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 10/15/2023] [Accepted: 11/13/2023] [Indexed: 11/20/2023]
Abstract
Metabolic flexibility refers to the ability of tissues to adapt their use of energy sources according to substrate availability and energy demands. This review aims to disentangle the emerging mechanisms through which altered metabolic flexibility and insulin resistance promote NAFLD and heart disease progression. Insulin resistance and metabolic inflexibility are central drivers of hepatic and cardiac diseases in individuals with type 2 diabetes. Both play a critical role in the complex interaction between glucose and lipid metabolism. Disruption of metabolic flexibility results in hyperglycemia and abnormal lipid metabolism, leading to increased accumulation of fat in the liver, contributing to the development and progression of NAFLD. Similarly, insulin resistance affects cardiac glucose metabolism, leading to altered utilization of energy substrates and impaired cardiac function, and influence cardiac lipid metabolism, further exacerbating the progression of heart failure. Regular physical activity promotes metabolic flexibility by increasing energy expenditure and enabling efficient switching between different energy substrates. On the contrary, weight loss achieved through calorie restriction ameliorates insulin sensitivity without improving flexibility. Strategies that mimic the effects of physical exercise, such as pharmacological interventions or targeted lifestyle modifications, show promise in effectively treating both diabetes and NAFLD, finally reducing the risk of advanced liver disease.
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Affiliation(s)
- Santo Colosimo
- School of Nutrition Science, University of Milan, Milan, Italy
| | - Sandip Kumar Mitra
- Diabetes and Endocrinology Unit, Apollo Gleneagles Hospital, Kolkata, West Bengal, India
| | - Tirthankar Chaudhury
- Diabetes and Endocrinology Unit, Apollo Gleneagles Hospital, Kolkata, West Bengal, India
| | - Giulio Marchesini
- IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola, Bologna, Italy.
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Swan D, Lisman T, Tripodi A, Thachil J. The prothrombotic tendency of metabolic-associated fatty liver disease. J Thromb Haemost 2023; 21:3045-3055. [PMID: 37353082 DOI: 10.1016/j.jtha.2023.06.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 05/12/2023] [Accepted: 06/12/2023] [Indexed: 06/25/2023]
Abstract
Our understanding of the function of the liver has evolved over the centuries. Early theories proposing that the liver could be used to divine the future have been superseded by our current knowledge of the importance of the liver in processes such as digestion and detoxification. Similarly, although liver disease was previously associated with only an increased risk of bleeding, there is now a substantial body of evidence demonstrating an increased thrombotic potential in patients with this disease. Metabolic-associated fatty liver disease (MAFLD) is increasing in frequency and is likely to overtake alcoholic liver disease as the primary indication for liver transplant in the future. In this review, we discuss the evidence linking liver disease, and MAFLD in particular, with arterial and venous thromboembolic disease. We review the safety and efficacy of anticoagulation in advanced liver disease and consider whether antithrombotic agents could slow or halt the progression of fibrosis in MAFLD.
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Affiliation(s)
- Dawn Swan
- Department of Haematology, Beaumont Hospital, Dublin, Ireland.
| | - Ton Lisman
- Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Armando Tripodi
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione Luigi Villa, Milano, Italy
| | - Jecko Thachil
- Department of Haematology, Manchester University Hospitals, Oxford Road, Manchester, UK
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Carli F, Sabatini S, Gaggini M, Sironi AM, Bedogni G, Gastaldelli A. Fatty Liver Index (FLI) Identifies Not Only Individuals with Liver Steatosis but Also at High Cardiometabolic Risk. Int J Mol Sci 2023; 24:14651. [PMID: 37834099 PMCID: PMC10572624 DOI: 10.3390/ijms241914651] [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: 08/13/2023] [Revised: 09/16/2023] [Accepted: 09/19/2023] [Indexed: 10/15/2023] Open
Abstract
A fatty liver index (FLI) greater than sixty (FLI ≥ 60) is an established score for metabolic dysfunction-associated steatotic liver disease (MASLD), which carries a high risk for diabetes and cardiovascular disease, while a FLI ≤ 20 rules out the presence of steatosis. Thus, we investigated whether FLI was associated with cardiometabolic risk factors, i.e., visceral (VAT), subcutaneous (SC), epicardial (EPI), extrapericardial (PERI), and total cardiac (CARD-AT) adipose tissue, hepatic fat ((by magnetic resonance imaging, MRI, and spectroscopy, MRS), and insulin resistance (IR, HOMA-IR and OGIS-index), and components of metabolic syndrome. All individuals with FLI ≥ 60 had MASLD, while none with FLI ≤ 20 had steatosis (by MRS). Subjects with FLI ≥ 60 had a higher BMI and visceral and cardiac fat (VAT > 1.7 kg, CARD-AT > 0.2 kg). FLI was positively associated with increased cardiac and visceral fat and components of metabolic syndrome. FLI, VAT, and CARD-AT were all associated with IR, increased blood pressure, cholesterol, and reduced HDL. For FLI ≥ 60, the cut-off values for fat depots and laboratory measures were estimated. In conclusion, FLI ≥ 60 identified not only subjects with steatosis but also those with IR, abdominal and cardiac fat accumulation, increased blood pressure, and hyperlipidemia, i.e., those at higher risk of cardiometabolic diseases. Targeted reduction of FLI components would help reduce cardiometabolic risk.
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Affiliation(s)
- Fabrizia Carli
- Cardiometabolic Risk Unit, Institute of Clinical Physiology, National Research Council (CNR), Via Giuseppe Moruzzi, 1, 56124 Pisa, Italy; (F.C.); (S.S.); (M.G.); (A.M.S.)
| | - Silvia Sabatini
- Cardiometabolic Risk Unit, Institute of Clinical Physiology, National Research Council (CNR), Via Giuseppe Moruzzi, 1, 56124 Pisa, Italy; (F.C.); (S.S.); (M.G.); (A.M.S.)
| | - Melania Gaggini
- Cardiometabolic Risk Unit, Institute of Clinical Physiology, National Research Council (CNR), Via Giuseppe Moruzzi, 1, 56124 Pisa, Italy; (F.C.); (S.S.); (M.G.); (A.M.S.)
| | - Anna Maria Sironi
- Cardiometabolic Risk Unit, Institute of Clinical Physiology, National Research Council (CNR), Via Giuseppe Moruzzi, 1, 56124 Pisa, Italy; (F.C.); (S.S.); (M.G.); (A.M.S.)
| | - Giorgio Bedogni
- Department of Medical and Surgical Sciences, University of Bologna, Via Zamboni, 33, 40126 Bologna, Italy
| | - Amalia Gastaldelli
- Cardiometabolic Risk Unit, Institute of Clinical Physiology, National Research Council (CNR), Via Giuseppe Moruzzi, 1, 56124 Pisa, Italy; (F.C.); (S.S.); (M.G.); (A.M.S.)
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8
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Yang K, Song M. New Insights into the Pathogenesis of Metabolic-Associated Fatty Liver Disease (MAFLD): Gut-Liver-Heart Crosstalk. Nutrients 2023; 15:3970. [PMID: 37764755 PMCID: PMC10534946 DOI: 10.3390/nu15183970] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 09/11/2023] [Accepted: 09/13/2023] [Indexed: 09/29/2023] Open
Abstract
Metabolism-associated fatty liver disease (MAFLD) is a multifaceted disease that involves complex interactions between various organs, including the gut and heart. It is defined by hepatic lipid accumulation and is related to metabolic dysfunction, obesity, and diabetes. Understanding the intricate interplay of the gut-liver-heart crosstalk is crucial for unraveling the complexities of MAFLD and developing effective treatment and prevention strategies. The gut-liver crosstalk participates in the regulation of the metabolic and inflammatory processes through host-microbiome interactions. Gut microbiota have been associated with the development and progression of MAFLD, and its dysbiosis contributes to insulin resistance, inflammation, and oxidative stress. Metabolites derived from the gut microbiota enter the systemic circulation and influence both the liver and heart, resulting in the gut-liver-heart axis playing an important role in MAFLD. Furthermore, growing evidence suggests that insulin resistance, endothelial dysfunction, and systemic inflammation in MAFLD may contribute to an increased risk of cardiovascular disease (CVD). Additionally, the dysregulation of lipid metabolism in MAFLD may also lead to cardiac dysfunction and heart failure. Overall, the crosstalk between the liver and heart involves a complex interplay of molecular pathways that contribute to the development of CVD in patients with MAFLD. This review emphasizes the current understanding of the gut-liver-heart crosstalk as a foundation for optimizing patient outcomes with MAFLD.
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Affiliation(s)
| | - Myeongjun Song
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea;
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9
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Armandi A, Bugianesi E. Extrahepatic Outcomes of Nonalcoholic Fatty Liver Disease: Cardiovascular Diseases. Clin Liver Dis 2023; 27:239-250. [PMID: 37024205 DOI: 10.1016/j.cld.2023.01.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
Abstract
Patients with nonalcoholic fatty liver disease (NAFLD) are at high risk of cardiovascular disease, including carotid atherosclerosis, coronary artery disease, heart failure, and arrhythmias. The risk is partially due to shared risk factors, but it may vary according to liver injury. A fatty liver may induce an atherogenic profile, the local necro-inflammatory changes of nonalcoholic steatohepatitis may enhance systemic metabolic inflammation, and fibrogenesis can run parallel in the liver and in the myocardium and precedes heart failure. The detrimental impact of a Western diet combines with polymorphisms in genes associated with atherogenic dyslipidemia. Shared clinical/diagnostic algorithms are needed to manage the cardiovascular risk in NAFLD.
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Affiliation(s)
- Angelo Armandi
- Department of Medical Sciences, University of Turin, Corso Dogliotti 14, Torino 10126, Italy
| | - Elisabetta Bugianesi
- Department of Medical Sciences, University of Turin, Corso Dogliotti 14, Torino 10126, Italy.
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10
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Adams LA. Cardiovascular disease in metabolic-associated fatty liver disease. Curr Opin Endocrinol Diabetes Obes 2023; 30:81-86. [PMID: 36779252 DOI: 10.1097/med.0000000000000803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/14/2023]
Abstract
PURPOSE OF REVIEW Fatty liver disease is increasingly common worldwide and is associated with an increased risk of cardiovascular disease (CVD). RECENT FINDINGS This review describes the cardiovascular outcomes, clinical assessment and management as well as the impact of emerging drug treatment on CVD risk. SUMMARY Patients with fatty liver require CVD risk assessment including consideration of statin therapy. Emerging therapeutic drugs for fatty liver may have both adverse and beneficial effects on CVD risk.
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Affiliation(s)
- Leon A Adams
- Medical School, University of Western Australia
- Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
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11
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Basheer S, Malik IR, Awan FR, Sughra K, Roshan S, Khalil A, Iqbal MJ, Parveen Z. Histological and Microscopic Analysis of Fats in Heart, Liver Tissue, and Blood Parameters in Experimental Mice. Genes (Basel) 2023; 14:515. [PMID: 36833442 PMCID: PMC9957320 DOI: 10.3390/genes14020515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 02/08/2023] [Accepted: 02/14/2023] [Indexed: 02/22/2023] Open
Abstract
The intake of various types and amounts of dietary fats influences metabolic and cardiovascular health. Hence, this study evaluated the impact of routinely consumed Pakistani dietary fats on their cardiometabolic impact. For this, we made four groups of mice, each comprising 5 animals: (1) C-ND: Control mice on a normal diet, (2) HFD-DG: High-fat diet mice on a normal diet plus 10% (w/w) desi ghee, (3) HFD-O: Mice on normal diet plus 10% (w/w) plant oil (4) HFD-BG: Mice on normal diet plus 10% (w/w) banaspati ghee. Mice were fed for 16 weeks, and blood, liver, and heart samples were collected for biochemical, histological, and electron microscopic analysis. The physical factors indicated that mice fed on HFD gained more body weight than the C-ND group. Blood parameters do not show significant differences, but overall, the glucose and cholesterol concentrations were raised in the mice fed with a fat-rich diet, with the highest concentrations in the HFD-BG group. The mice fed with HFD-BG and HFD-O had more lipid droplets in the liver, compared to HFD-DG and C-ND.
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Affiliation(s)
- Sehrish Basheer
- Department of Biotechnology, University of Sargodha, Sargodha 40100, Pakistan
- Diabetes and Cardio-Metabolic Disorders Lab, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Jhang Road, Faisalabad 38000, Pakistan
| | - Imran Riaz Malik
- Department of Biotechnology, University of Sargodha, Sargodha 40100, Pakistan
| | - Fazli Rabbi Awan
- Diabetes and Cardio-Metabolic Disorders Lab, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Jhang Road, Faisalabad 38000, Pakistan
| | - Kalsoom Sughra
- Department of Biochemistry and Biotechnology, University of Gujrat, Gujrat 50700, Pakistan
| | - Sadia Roshan
- Department of Zoology, University of Gujrat, Gujrat 50700, Pakistan
| | - Adila Khalil
- Diabetes and Cardio-Metabolic Disorders Lab, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Jhang Road, Faisalabad 38000, Pakistan
| | - Muhammad Javed Iqbal
- Diabetes and Cardio-Metabolic Disorders Lab, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Jhang Road, Faisalabad 38000, Pakistan
| | - Zahida Parveen
- Department of Biochemistry, Abdul Wali Khan University, Mardan 23200, Pakistan
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12
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Manikat R, Nguyen MH. Nonalcoholic fatty liver disease and non-liver comorbidities. Clin Mol Hepatol 2023; 29:s86-s102. [PMID: 36603574 PMCID: PMC10029963 DOI: 10.3350/cmh.2022.0442] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 12/28/2022] [Accepted: 01/03/2023] [Indexed: 01/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by excess fat accumulation in the liver. It is closely associated with metabolic syndrome, and patients with NAFLD often have comorbidities such as obesity, type 2 diabetes mellitus, and dyslipidemia. In addition to liver-related complications, NAFLD has been associated with a range of non-liver comorbidities, including cardiovascular disease, chronic kidney disease, and sleep apnea. Cardiovascular disease is the most common cause of mortality in patients with NAFLD, and patients with NAFLD have a higher risk of developing cardiovascular disease than the general population. Chronic kidney disease is also more common in patients with NAFLD, and the severity of NAFLD is associated with a higher risk of developing chronic kidney disease. Sleep apnea, a disorder characterized by breathing interruptions during sleep, is also more common in patients with NAFLD and is associated with the severity of NAFLD. The presence of non-liver comorbidities in patients with NAFLD has important implications for the management of this disease. Treatment of comorbidities such as obesity, type 2 diabetes mellitus, and dyslipidemia may improve liver-related outcomes in patients with NAFLD. Moreover, treatment of non-liver comorbidities may also improve overall health outcomes in patients with NAFLD. Therefore, clinicians should be aware of the potential for non-liver comorbidities in patients with NAFLD and should consider the management of these comorbidities as part of the overall management of this disease.
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Affiliation(s)
- Richie Manikat
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
- Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USA
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13
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Keles U, Ow JR, Kuentzel KB, Zhao LN, Kaldis P. Liver-derived metabolites as signaling molecules in fatty liver disease. Cell Mol Life Sci 2022; 80:4. [PMID: 36477411 PMCID: PMC9729146 DOI: 10.1007/s00018-022-04658-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 11/25/2022] [Accepted: 11/26/2022] [Indexed: 12/12/2022]
Abstract
Excessive fat accumulation in the liver has become a major health threat worldwide. Unresolved fat deposition in the liver can go undetected until it develops into fatty liver disease, followed by steatohepatitis, fibrosis, cirrhosis, and eventually hepatocellular carcinoma. Lipid deposition in the liver is governed by complex communication, primarily between metabolic organs. This can be mediated by hormones, organokines, and also, as has been more recently discovered, metabolites. Although how metabolites from peripheral organs affect the liver is well documented, the effect of metabolic players released from the liver during the development of fatty liver disease or associated comorbidities needs further attention. Here we focus on interorgan crosstalk based on metabolites released from the liver and how these molecules act as signaling molecules in peripheral tissues. Due to the liver's specific role, we are covering lipid and bile mechanism-derived metabolites. We also discuss the high sucrose intake associated with uric acid release from the liver. Excessive fat deposition in the liver during fatty liver disease development reflects disrupted metabolic processes. As a response, the liver secretes a variety of signaling molecules as well as metabolites which act as a footprint of the metabolic disruption. In the coming years, the reciprocal exchange of metabolites between the liver and other metabolic organs will gain further importance and will help to better understand the development of fatty liver disease and associated diseases.
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Affiliation(s)
- Umur Keles
- Department of Clinical Sciences, Clinical Research Centre (CRC), Lund University, Box 50332, 202 13, Malmö, Sweden
| | - Jin Rong Ow
- Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), 61 Biopolis Drive, Proteos, Singapore, 138673, Republic of Singapore
| | - Katharina Barbara Kuentzel
- Department of Clinical Sciences, Clinical Research Centre (CRC), Lund University, Box 50332, 202 13, Malmö, Sweden
| | - Li Na Zhao
- Department of Clinical Sciences, Clinical Research Centre (CRC), Lund University, Box 50332, 202 13, Malmö, Sweden
| | - Philipp Kaldis
- Department of Clinical Sciences, Clinical Research Centre (CRC), Lund University, Box 50332, 202 13, Malmö, Sweden. .,Lund University Diabetes Centre (LUDC), Clinical Research Centre (CRC), Lund University, Box 50332, 202 13, Malmö, Sweden.
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14
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Systematic Review and Meta-Analysis of the Usefulness of Epicardial Fat Thickness as a Non-Invasive Marker of the Presence and Severity of Nonalcoholic Fatty Liver Disease. Biomedicines 2022; 10:biomedicines10092204. [PMID: 36140303 PMCID: PMC9496452 DOI: 10.3390/biomedicines10092204] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 07/12/2022] [Accepted: 09/01/2022] [Indexed: 11/17/2022] Open
Abstract
We performed a systematic review and meta-analysis to assess the association between epicardial fat thickness (EFT) and nonalcoholic fatty liver disease (NAFLD). This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) and was based on a registered protocol (CRD 4201809 5493). We searched Medline and Embase until December 2021 for studies reporting on the association between EFT and NAFLD. Qualitative reviews, meta-analyses and meta-regressions were performed to explore this association. Effect sizes are reported as standardized mean differences. We included 12 studies, comprising 3610 individuals. EFT was evaluated with trans-thoracic echocardiography in nine studies, two studies using cardiac computed tomography and one study using magnetic resonance imaging (MRI). The presence of NAFLD was evaluated using transabdominal liver ultrasound in nine studies. Other studies used histology, magnetic resonance spectroscopy and MRI-derived proton density fat fraction. Liver biopsy was performed to assess the severity of NAFLD in four studies. The random-effects meta-analysis indicated that, as compared to control patients with lean livers, patients with NAFLD displayed significantly higher EFT (standardized mean difference 0.61, 95% confidence interval: 0.47−0.75, p < 0.0001, I2 = 72%). EFT was further significantly higher in patients with severe liver steatosis versus patients with mild−moderate liver steatosis (standardized mean difference 1.21 95% confidence interval: 0.26−2.16, p < 0.001, I2 S = 96%). Through the meta-regression analysis, we found that patients with increasingly higher blood levels of aspartate aminotransferase displayed an increasingly higher depth of association. The current meta-analysis suggests that EFT may represent a useful surrogate for assessing the presence and severity of NAFLD in a non-invasive manner.
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15
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Li W, Wen W, Xie D, Qiu M, Cai X, Zheng S, Huang Y. Association between non-alcoholic fatty liver disease and risk of incident heart failure: a meta-analysis of observational studies. Ther Adv Chronic Dis 2022; 13:20406223221119626. [PMID: 36052287 PMCID: PMC9425885 DOI: 10.1177/20406223221119626] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 07/27/2022] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND AND AIMS Recent research has associated non-alcoholic fatty liver disease (NAFLD) with an increased risk of atherosclerotic cardiovascular disease. Previous studies that evaluated the association between NAFLD and risk of heart failure (HF) yielded inconsistent results, however. This meta-analysis aimed to evaluate the association between NAFLD and the risk of HF. METHODS We searched multiple electronic databases, including PubMed, Google Scholar, Embase and Web of Science for potential studies published from inception until 30 October 2021. Cohort studies reported multivariable-adjusted risks of incident HF in NAFLD patients comparing those without NAFLD were included. RESULTS Six cohort studies comprising 10,979,967 participants (women = 55.5%) were included in the study. The median prevalence of NAFLD in these studies was 22.2%. During a median follow-up duration of 7.0 years, 92,915 HF cases were detected. In the unadjusted model, patients with NAFLD had a greater risk of incident HF [random-effect hazard ratio (HR) = 1.47, 95% confidence interval (CI) = 1.25-1.75, I 2 = 99%], compared with those without NAFLD. After multivariable adjustment of confounding risk factors, NAFLD was still linked with a higher risk of HF incidence (random-effect HR = 1.36, 95% CI = 1.16-1.58, I 2 = 98%). The risk of HF was increased not only in patients with progressive NAFLD severity but also in those with simple steatosis. The absolute risk difference of HF in NAFLD patients compared with those without NAFLD was 11.0 (95% CI = 4.9-17.7) per 10,000 person-years after multivariable adjustment. CONCLUSION This meta-analysis suggests that NAFLD may be associated with an increased risk of incident HF. Owing to the high heterogeneity of the published studies, however, further high-quality studies are still needed.
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Affiliation(s)
- Wensheng Li
- Department of Cardiology, Shunde Hospital, Southern Medical University (the First People’s Hospital of Shunde), Foshan, China
| | - Weixing Wen
- Department of Cardiology, Shunde Hospital, Southern Medical University (the First People’s Hospital of Shunde), Foshan, China
| | - Dongxiao Xie
- Department of Cardiology, Shunde Hospital, Southern Medical University (the First People’s Hospital of Shunde), Foshan, China
| | - Min Qiu
- Department of Cardiology, Shunde Hospital, Southern Medical University (the First People’s Hospital of Shunde), Foshan, China
| | - Xiaoyan Cai
- Department of Scientific Research and Education, Shunde Hospital, Southern Medical University (the First People’s Hospital of Shunde), Foshan, China
| | - Sulin Zheng
- Department of Cardiology, Shunde Hospital, Southern Medical University (the First People’s Hospital of Shunde), Foshan, China
| | - Yuli Huang
- Department of Cardiology, Shunde Hospital, Southern Medical University (the First People’s Hospital of Shunde), Jiazhi Road, Lunjiao Town, Shunde District, Foshan 528300, China
- The George Institute for Global Health, Faculty of Medicine, University of New South Wales Sydney, Sydney, NSW, Australia
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Edin C, Ekstedt M, Scheffel T, Karlsson M, Swahn E, Östgren CJ, Engvall J, Ebbers T, Leinhard OD, Lundberg P, Carlhäll CJ. Ectopic fat is associated with cardiac remodeling—A comprehensive assessment of regional fat depots in type 2 diabetes using multi-parametric MRI. Front Cardiovasc Med 2022; 9:813427. [PMID: 35966535 PMCID: PMC9366177 DOI: 10.3389/fcvm.2022.813427] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 06/30/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundDifferent regional depots of fat have distinct metabolic properties and may relate differently to adverse cardiac remodeling. We sought to quantify regional depots of body fat and to investigate their relationship to cardiac structure and function in Type 2 Diabetes (T2D) and controls.MethodsFrom the SCAPIS cohort in Linköping, Sweden, we recruited 92 subjects (35% female, mean age 59.5 ± 4.6 years): 46 with T2D and 46 matched controls. In addition to the core SCAPIS data collection, participants underwent a comprehensive magnetic resonance imaging examination at 1.5 T for assessment of left ventricular (LV) structure and function (end-diastolic volume, mass, concentricity, ejection fraction), as well as regional body composition (liver proton density fat fraction, visceral adipose tissue, abdominal subcutaneous adipose tissue, thigh muscle fat infiltration, fat tissue-free thigh muscle volume and epicardial adipose tissue).ResultsCompared to the control group, the T2D group had increased: visceral adipose tissue volume index (P < 0.001), liver fat percentage (P < 0.001), thigh muscle fat infiltration percentage (P = 0.02), LV concentricity (P < 0.001) and LV E/e'-ratio (P < 0.001). In a multiple linear regression analysis, a negative association between liver fat percentage and LV mass (St Beta −0.23, P < 0.05) as well as LV end-diastolic volume (St Beta −0.27, P < 0.05) was found. Epicardial adipose tissue volume and abdominal subcutaneous adipose tissue volume index were the only parameters of fat associated with LV diastolic dysfunction (E/e'-ratio) (St Beta 0.24, P < 0.05; St Beta 0.34, P < 0.01, respectively). In a multivariate logistic regression analysis, only visceral adipose tissue volume index was significantly associated with T2D, with an odds ratio for T2D of 3.01 (95% CI 1.28–7.05, P < 0.05) per L/m2 increase in visceral adipose tissue volume.ConclusionsEctopic fat is predominantly associated with cardiac remodeling, independently of type 2 diabetes. Intriguingly, liver fat appears to be related to LV structure independently of VAT, while epicardial fat is linked to impaired LV diastolic function. Visceral fat is associated with T2D independently of liver fat and abdominal subcutaneous adipose tissue.
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Affiliation(s)
- Carl Edin
- Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- *Correspondence: Carl Edin
| | - Mattias Ekstedt
- Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Department of Gastroenterology in Linköping and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
- Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden
| | - Tobias Scheffel
- Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Markus Karlsson
- Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden
- AMRA Medical AB, Linköping University, Linköping, Sweden
- Department of Radiation Physics and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Eva Swahn
- Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Department of Cardiology in Linköping and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Carl Johan Östgren
- Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden
- Division of Prevention, Rehabilitation and Community Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Jan Engvall
- Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden
- Department of Clinical Physiology in Linköping and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Tino Ebbers
- Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden
| | - Olof Dahlqvist Leinhard
- Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden
- AMRA Medical AB, Linköping University, Linköping, Sweden
- Department of Radiation Physics and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Peter Lundberg
- Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden
- Department of Radiation Physics and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Carl-Johan Carlhäll
- Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden
- Department of Clinical Physiology in Linköping and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
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Ciardullo S, Oltolini A, Cannistraci R, Muraca E, Perseghin G. Sex-related association of nonalcoholic fatty liver disease and liver fibrosis with body fat distribution in the general US population. Am J Clin Nutr 2022; 115:1528-1534. [PMID: 35244676 DOI: 10.1093/ajcn/nqac059] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 03/02/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Few population-based studies have investigated the association between body fat distribution and the risk of nonalcoholic fatty liver disease (NAFLD) and significant liver fibrosis. OBJECTIVES We aimed to evaluate the relations of total body fat and body fat distribution with NAFLD in the general US population. METHODS This is a cross-sectional, population-based study based on the 2017-2018 cycle of the NHANES. Participants aged 18-59 y without known liver conditions or significant alcohol consumption were studied by DXA and vibration-controlled transient elastography to assess body composition and liver steatosis and fibrosis, respectively. Multivariable logistic regression analysis was performed to evaluate the contribution of BMI and android:gynoid ratio (A:G ratio) to the prevalence of liver steatosis and fibrosis in males and females. RESULTS Weighted prevalence of steatosis was 41.5% and 29.9% among the 1115 males and 1113 females included in the study, respectively, whereas 7.0% of males and 4.0% of females had elastographic evidence of significant liver fibrosis. After adjustment for age, race-Hispanic origin, diabetes, cigarette smoke, and BMI, a higher A:G ratio was associated with increased odds of steatosis in both males (OR: 1.79; 95% CI: 1.07, 2.99; P = 0.029) and females (OR: 1.95; 95% CI: 1.11, 3.41; P = 0.023). Conversely, a significant association between A:G ratio and liver fibrosis was identified in females (OR: 2.09; 95% CI: 1.11, 3.97; P = 0.026), but not in males (OR: 0.56; 95% CI: 0.29, 1.08; P = 0.078). CONCLUSIONS Independently from BMI, an android fat deposition pattern is associated with increased prevalence of NAFLD in both sexes, whereas the effect on fibrosis was only evident in females.
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Affiliation(s)
- Stefano Ciardullo
- Department of Medicine and Rehabilitation, Monza Polyclinic, Monza, Italy.,Department of Medicine and Surgery, University of Milan Bicocca, Milan, Italy
| | - Alice Oltolini
- Department of Medicine and Rehabilitation, Monza Polyclinic, Monza, Italy
| | - Rosa Cannistraci
- Department of Medicine and Rehabilitation, Monza Polyclinic, Monza, Italy.,Department of Medicine and Surgery, University of Milan Bicocca, Milan, Italy
| | - Emanuele Muraca
- Department of Medicine and Rehabilitation, Monza Polyclinic, Monza, Italy
| | - Gianluca Perseghin
- Department of Medicine and Rehabilitation, Monza Polyclinic, Monza, Italy.,Department of Medicine and Surgery, University of Milan Bicocca, Milan, Italy
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18
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Minhas AMK, Bhopalwala HM, Dewaswala N, Salah HM, Khan MS, Shahid I, Biegus J, Lopes RD, Pandey A, Fudim M. Association of Non-Alcoholic Fatty Liver Disease with In-Hospital Outcomes in Primary Heart Failure Hospitalizations with Reduced or Preserved Ejection Fraction. Curr Probl Cardiol 2022:101199. [DOI: 10.1016/j.cpcardiol.2022.101199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 04/02/2022] [Indexed: 11/03/2022]
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19
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Pericardial fat, thoracic peri-aortic adipose tissue, and systemic inflammatory marker in nonalcoholic fatty liver and abdominal obesity phenotype. Sci Rep 2022; 12:1958. [PMID: 35121786 PMCID: PMC8816900 DOI: 10.1038/s41598-022-06030-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 01/17/2022] [Indexed: 12/24/2022] Open
Abstract
Researchers have conducted many studies about the relationships between peri-cardiovascular fat, nonalcoholic fatty liver disease (NAFLD), waist circumference, and cardiovascular disease (CVD). Nevertheless, the relationship between NAFLD and pericardial fat (PCF)/thoracic peri-aortic adipose tissue (TAT) phenotypes was still unknown. This study aimed to explore whether PCF/TAT was associated with NAFLD/abdominal obesity (AO) phenotypes in different high-sensitivity C-reactive protein (hs-CRP) levels. We consecutively studied 1655 individuals (mean age, 49.44 ± 9.76 years) who underwent a health-screening program. We showed a significant association between PCF/TAT and NAFLD/AO phenotypes in the cross-sectional study. We observed that the highest risk occurred in both abnormalities' groups, and the second highest risk occurred in the AO-only group. Subjects with AO had a significantly increased risk of PCF or TAT compared to those with NAFLD. Notably, the magnitude of the associations between PCF/TAT and NAFLD/AO varied by the level of systemic inflammatory marker (hs-CRP level). We suggested that people with AO and NAFLD must be more careful about changes in PCF and TAT. Regular measurement of waist circumference (or AO) can be a more accessible way to monitor peri-cardiovascular fat (PCF and TAT), which may serve as a novel and rapid way to screen CVD in the future.
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20
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Is NMDA-Receptor-Mediated Oxidative Stress in Mitochondria of Peripheral Tissues the Essential Factor in the Pathogenesis of Hepatic Encephalopathy? J Clin Med 2022; 11:jcm11030827. [PMID: 35160278 PMCID: PMC8836479 DOI: 10.3390/jcm11030827] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 02/01/2022] [Accepted: 02/03/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome of increased ammonia-mediated brain dysfunction caused by impaired hepatic detoxification or when the blood bypasses the liver. Ammonia-activated signal transduction pathways of hyperactivated NMDA receptors (NMDAR) are shown to trigger a cascade of pathological reactions in the brain, leading to oxidative stress. NMDARs outside the brain are widely distributed in peripheral tissues, including the liver, heart, pancreas, and erythrocytes. To determine the contribution of these receptors to ammonia-induced oxidative stress in peripheral tissues, it is relevant to investigate if there are any ammonia-related changes in antioxidant enzymes and free radical formation and whether blockade of NMDARs prevents these changes. Methods: Hyperammonemia was induced in rats by ammonium acetate injection. Oxidative stress was measured as changes in antioxidant enzyme activities and O2•− and H2O2 production by mitochondria isolated from the tissues and cells mentioned above. The effects of the NMDAR antagonist MK-801 on oxidative stress markers and on tissue ammonia levels were evaluated. Results: Increased ammonia levels in erythrocytes and mitochondria isolated from the liver, pancreas, and heart of hyperammonemic rats are shown to cause tissue-specific oxidative stress, which is prevented completely (or partially in erythrocyte) by MK-801. Conclusions: These results support the view that the pathogenesis of HE is multifactorial and that ammonia-induced multiorgan oxidative stress-mediated by activation of NMDAR is an integral part of the disease and, therefore, the toxic effects of ammonia in НЕ may be more global than initially expected.
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21
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Daudé P, Ancel P, Confort Gouny S, Jacquier A, Kober F, Dutour A, Bernard M, Gaborit B, Rapacchi S. Deep-Learning Segmentation of Epicardial Adipose Tissue Using Four-Chamber Cardiac Magnetic Resonance Imaging. Diagnostics (Basel) 2022; 12:126. [PMID: 35054297 PMCID: PMC8774679 DOI: 10.3390/diagnostics12010126] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 12/29/2021] [Accepted: 12/29/2021] [Indexed: 12/24/2022] Open
Abstract
In magnetic resonance imaging (MRI), epicardial adipose tissue (EAT) overload remains often overlooked due to tedious manual contouring in images. Automated four-chamber EAT area quantification was proposed, leveraging deep-learning segmentation using multi-frame fully convolutional networks (FCN). The investigation involved 100 subjects-comprising healthy, obese, and diabetic patients-who underwent 3T cardiac cine MRI, optimized U-Net and FCN (noted FCNB) were trained on three consecutive cine frames for segmentation of central frame using dice loss. Networks were trained using 4-fold cross-validation (n = 80) and evaluated on an independent dataset (n = 20). Segmentation performances were compared to inter-intra observer bias with dice (DSC) and relative surface error (RSE). Both systole and diastole four-chamber area were correlated with total EAT volume (r = 0.77 and 0.74 respectively). Networks' performances were equivalent to inter-observers' bias (EAT: DSCInter = 0.76, DSCU-Net = 0.77, DSCFCNB = 0.76). U-net outperformed (p < 0.0001) FCNB on all metrics. Eventually, proposed multi-frame U-Net provided automated EAT area quantification with a 14.2% precision for the clinically relevant upper three quarters of EAT area range, scaling patients' risk of EAT overload with 70% accuracy. Exploiting multi-frame U-Net in standard cine provided automated EAT quantification over a wide range of EAT quantities. The method is made available to the community through a FSLeyes plugin.
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Affiliation(s)
- Pierre Daudé
- Aix-Marseille Univ, CNRS, CRMBM, 13005 Marseille, France; (S.C.G.); (A.J.); (F.K.); (M.B.)
- APHM, Hôpital Universitaire Timone, CEMEREM, 13385 Marseille, France
| | - Patricia Ancel
- Department of Radiology, APHM, La Timone Hospital, 13005 Marseille, France;
- Aix-Marseille Univ, INSERM, INRAE, C2VN, 13005 Marseille, France; (A.D.); (B.G.)
| | - Sylviane Confort Gouny
- Aix-Marseille Univ, CNRS, CRMBM, 13005 Marseille, France; (S.C.G.); (A.J.); (F.K.); (M.B.)
- APHM, Hôpital Universitaire Timone, CEMEREM, 13385 Marseille, France
| | - Alexis Jacquier
- Aix-Marseille Univ, CNRS, CRMBM, 13005 Marseille, France; (S.C.G.); (A.J.); (F.K.); (M.B.)
- APHM, Hôpital Universitaire Timone, CEMEREM, 13385 Marseille, France
- Department of Radiology, APHM, La Timone Hospital, 13005 Marseille, France;
| | - Frank Kober
- Aix-Marseille Univ, CNRS, CRMBM, 13005 Marseille, France; (S.C.G.); (A.J.); (F.K.); (M.B.)
- APHM, Hôpital Universitaire Timone, CEMEREM, 13385 Marseille, France
| | - Anne Dutour
- Aix-Marseille Univ, INSERM, INRAE, C2VN, 13005 Marseille, France; (A.D.); (B.G.)
- Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle ENDO, APHM, Hôpital Nord, Chemin Des Bourrely, 13005 Marseille, France
| | - Monique Bernard
- Aix-Marseille Univ, CNRS, CRMBM, 13005 Marseille, France; (S.C.G.); (A.J.); (F.K.); (M.B.)
- APHM, Hôpital Universitaire Timone, CEMEREM, 13385 Marseille, France
| | - Bénédicte Gaborit
- Aix-Marseille Univ, INSERM, INRAE, C2VN, 13005 Marseille, France; (A.D.); (B.G.)
- Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle ENDO, APHM, Hôpital Nord, Chemin Des Bourrely, 13005 Marseille, France
| | - Stanislas Rapacchi
- Aix-Marseille Univ, CNRS, CRMBM, 13005 Marseille, France; (S.C.G.); (A.J.); (F.K.); (M.B.)
- APHM, Hôpital Universitaire Timone, CEMEREM, 13385 Marseille, France
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22
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Garbuzenko DV, Belov DV. Non-alcoholic fatty liver disease as an independent factor of cardiometabolic risk of cardiovascular diseases. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2021:22-34. [DOI: 10.31146/1682-8658-ecg-194-10-22-34] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a pressing public health problem affecting up to a third of the world's adult population. The main reasons for its high mortality rate are cardiovascular diseases. They are caused by subclinical atherosclerosis characteristic of NAFLD, venous thromboembolic complications, functional and structural myocardial disorders, calcification of heart valves, heart rhythm and conduction disturbances. At the same time, NAFLD can serve as an independent factor of the cardiometabolic risk of their development, which is associated with atherogenic dyslipidemia, as well as the release of numerous pro-inflammatory mediators both from the pathologically altered liver and as a result of systemic endotoxemia, which is the result of disturbance of the intestinal microbiota, accompanied by a decrease in intestinal microbial gene richness., a change in its composition and function, followed by bacterial translocation. Considering that most patients with NAFLD die from cardiovascular complications, it becomes obvious that exclusively “liver-oriented” principles of their treatment cannot be sufficient, but require a multidisciplinary team approach involving cardiologists, cardiac surgeons and doctors of other related specialties.
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23
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Salah HM, Pandey A, Soloveva A, Abdelmalek MF, Diehl AM, Moylan CA, Wegermann K, Rao VN, Hernandez AF, Tedford RJ, Parikh KS, Mentz RJ, McGarrah RW, Fudim M. Relationship of Nonalcoholic Fatty Liver Disease and Heart Failure With Preserved Ejection Fraction. JACC Basic Transl Sci 2021; 6:918-932. [PMID: 34869957 PMCID: PMC8617573 DOI: 10.1016/j.jacbts.2021.07.010] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 07/27/2021] [Accepted: 07/27/2021] [Indexed: 12/17/2022]
Abstract
Although there is an established bidirectional relationship between heart failure with reduced ejection fraction and liver disease, the association between heart failure with preserved ejection fraction (HFpEF) and liver diseases, such as nonalcoholic fatty liver disease (NAFLD), has not been well explored. In this paper, the authors provide an in-depth review of the relationship between HFpEF and NAFLD and propose 3 NAFLD-related HFpEF phenotypes (obstructive HFpEF, metabolic HFpEF, and advanced liver fibrosis HFpEF). The authors also discuss diagnostic challenges related to the concurrent presence of NAFLD and HFpEF and offer several treatment options for NAFLD-related HFpEF phenotypes. The authors propose that NAFLD-related HFpEF should be recognized as a distinct HFpEF phenotype.
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Key Words
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- AV, arteriovenous
- BCAA, branched-chain amino acid
- GLP, glucagon-like peptide
- HF, heart failure
- HFpEF
- HFpEF, heart failure with preserved ejection fraction
- HFrEF, heart failure with reduced ejection fraction
- IL, interleukin
- LV, left ventricular
- LVEF, left ventricular ejection fraction
- NAFLD
- NAFLD, nonalcoholic fatty liver disease
- NASH, nonalcoholic steatohepatitis
- NT-proBNP, N terminal pro–B-type natriuretic peptide
- RAAS, renin-angiotensin aldosterone system
- SGLT2, sodium-glucose cotransporter 2
- SPSS, spontaneous portosystemic shunt(s)
- TNF, tumor necrosis factor
- cardiomyopathy
- heart failure
- liver
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Affiliation(s)
- Husam M. Salah
- Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
| | - Ambarish Pandey
- Division of Cardiology, Department of Medicine, University of Texas Southwestern, and Parkland Health and Hospital System, Dallas, Texas, USA
| | - Anzhela Soloveva
- Department of Cardiology, Almazov National Medical Research Centre, Saint Petersburg, Russian Federation
| | - Manal F. Abdelmalek
- Division of Gastroenterology and Hepatology, Duke University, Durham, North Carolina, USA
| | - Anna Mae Diehl
- Division of Gastroenterology and Hepatology, Duke University, Durham, North Carolina, USA
| | - Cynthia A. Moylan
- Division of Gastroenterology and Hepatology, Duke University, Durham, North Carolina, USA
| | - Kara Wegermann
- Division of Gastroenterology and Hepatology, Duke University, Durham, North Carolina, USA
| | - Vishal N. Rao
- Division of Cardiology, Department of Medicine, Duke University, Durham, North Carolina, USA
- Duke Clinical Research Institute, Durham, North Carolina, USA
| | - Adrian F. Hernandez
- Division of Cardiology, Department of Medicine, Duke University, Durham, North Carolina, USA
- Duke Clinical Research Institute, Durham, North Carolina, USA
| | - Ryan J. Tedford
- Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Kishan S. Parikh
- Division of Cardiology, Department of Medicine, Duke University, Durham, North Carolina, USA
| | - Robert J. Mentz
- Division of Cardiology, Department of Medicine, Duke University, Durham, North Carolina, USA
- Duke Clinical Research Institute, Durham, North Carolina, USA
| | - Robert W. McGarrah
- Division of Cardiology, Department of Medicine, Duke University, Durham, North Carolina, USA
| | - Marat Fudim
- Division of Cardiology, Department of Medicine, Duke University, Durham, North Carolina, USA
- Duke Clinical Research Institute, Durham, North Carolina, USA
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24
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Møller S, Kimer N, Kronborg T, Grandt J, Hove JD, Barløse M, Gluud LL. Nonalcoholic Fatty Liver Disease and Cardiovascular Disease: Overlapping Mechanisms. Semin Liver Dis 2021; 41:235-247. [PMID: 33992031 DOI: 10.1055/s-0041-1725022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) denotes a condition with excess fat in the liver. The prevalence of NAFLD is increasing, averaging > 25% of the Western population. In 25% of the patients, NAFLD progresses to its more severe form: nonalcoholic steatohepatitis and >25% of these progress to cirrhosis following activation of inflammatory and fibrotic processes. NAFLD is associated with obesity, type 2 diabetes, and the metabolic syndrome and represents a considerable and increasing health burden. In the near future, NAFLD cirrhosis is expected to be the most common cause for liver transplantation. NAFLD patients have an increased risk of developing cardiovascular disease as well as liver-related morbidity. In addition, hepatic steatosis itself appears to represent an independent cardiovascular risk factor. In the present review, we provide an overview of the overlapping mechanisms and prevalence of NAFLD and cardiovascular disease.
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Affiliation(s)
- Søren Møller
- Department of Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark.,Department of Clinical Medicine, University of Copenhagen, Denmark
| | - Nina Kimer
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Denmark.,Bridge Translational Excellence Program, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark
| | - Thit Kronborg
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Denmark
| | - Josephine Grandt
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Denmark
| | - Jens Dahlgaard Hove
- Department of Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark.,Department of Cardiology, Copenhagen University Hospital, Hvidovre, Denmark
| | - Mads Barløse
- Department of Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark
| | - Lise Lotte Gluud
- Department of Clinical Medicine, University of Copenhagen, Denmark.,Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Denmark
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Ciardullo S, Bianconi E, Zerbini F, Perseghin G. Current type 2 diabetes, rather than previous gestational diabetes, is associated with liver disease in U.S. Women. Diabetes Res Clin Pract 2021; 177:108879. [PMID: 34058299 DOI: 10.1016/j.diabres.2021.108879] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 05/13/2021] [Accepted: 05/26/2021] [Indexed: 12/19/2022]
Abstract
AIM To investigate the relative contribution of previous gestational diabetes mellitus (GDM) and current type 2 diabetes (T2D) on the development of liver fibrosis, the strongest predictor of end-stage liver disease. METHODS This is a population-based cross-sectional study based on data from the 2017-2018 cycle of the National Health and Nutrition Examination Survey. We included women age ≥ 20 years that had delivered at least one live birth and had available data on vibration-controlled transient elastography (VCTE). Liver steatosis and fibrosis were assessed by the median value of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. RESULTS Among the 1699 women included in the study, 144 (10.1%, 95% CI 7.7-13.2) reported a previous diagnosis of GDM. Women with previous GDM were younger, had a higher BMI, a higher prevalence of T2D and were significantly older at the time they had the last live birth. Univariate analysis did not show a significant difference between women with and without a prior history of GDM in terms of both steatosis (44.8% vs 39.4%, p = 0.464) and fibrosis (7.5% vs 7.6%, p = 0.854). Multivariable logistic regression analysis showed that BMI, γ-glutamyltranspeptidase levels, T2D (OR 2.96, 95% CI 1.48-5.93, p < 0.01), HBV and HCV infection were associated with higher odds of significant fibrosis, while previous GDM showed a neutral effect. CONCLUSIONS Women with previous GDM that do not develop overt T2D might not experience a poor hepatic prognosis.
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Affiliation(s)
- Stefano Ciardullo
- Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy; Department of Medicine and Surgery, University of Milano Bicocca, Milan, Italy
| | - Eleonora Bianconi
- Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy
| | - Francesca Zerbini
- Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy
| | - Gianluca Perseghin
- Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy; Department of Medicine and Surgery, University of Milano Bicocca, Milan, Italy.
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26
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Different body parts' fat mass and corrected QT interval on the electrocardiogram: The Fasa PERSIAN Cohort Study. BMC Cardiovasc Disord 2021; 21:277. [PMID: 34090333 PMCID: PMC8178852 DOI: 10.1186/s12872-021-02095-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 06/01/2021] [Indexed: 11/15/2022] Open
Abstract
Background Previous studies suggested that obesity and fat mass are associated with QT interval prolongation, but the role of different body parts' fat mass is unclear. The associations between total and regional fat mass (FM) and corrected QT interval (QTc) were investigated for the first time in this study.
Methods In this sub-analysis of Fasa PERSIAN cohort Study data, 3217 subjects aged 35–70 entered our study. Body fat mass was assessed by bioelectrical impedance analysis and QTc interval calculated by the QT interval measured by Cardiax® software from ECGs and Bazett’s formula. Uni- and multi-variable linear and logistic regression was performed in IBM SPSS Statistics v23. Results In males, the fat mass to fat-free mass (FM/FFM) ratio in the trunk, arms, total body, and legs were significantly higher in the prolonged QTc group (QTc > 450 ms). Trunk (B = 0.148), total (B = 0.137), arms (B = 0.124), legs (B = 0.107) fat mass index (FMI) showed significant positive relationship with continuous QTc (P-value < 0.001). Also, just the fat-free mass index of legs had significant positive associations with QTc interval (P-value < 0.05). Surprisingly, in females, the mean of FM/FFM ratio in trunk and legs in the normal QTc group had higher values than the prolonged QTc group (QTc > 470 ms). Also, none of the body composition variables had a significant correlation with continuous QTc. Conclusion Our study suggested that FMI ratios in the trunk, total body, arms, and legs were positively associated with QTc interval in males, respectively, from a higher to a lower beta-coefficient. Such associations were not seen in females. Our study implies that body fat mass may be an independent risk factor for higher QTc interval and, consequently, more cardiovascular events that should be investigated. Supplementary Information The online version contains supplementary material available at 10.1186/s12872-021-02095-2.
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27
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Armandi A, Bugianesi E. Natural history of NASH. Liver Int 2021; 41 Suppl 1:78-82. [PMID: 34155792 PMCID: PMC8361694 DOI: 10.1111/liv.14910] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 04/20/2021] [Accepted: 04/20/2021] [Indexed: 12/12/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the fastest growing cause of chronic liver disease worldwide. Although only a small proportion of NAFLD patients will progress to end-stage liver disease and death, the clinical burden of NAFLD is substantial due the sheer number of individuals affected worldwide. In fact, recent estimates suggest that 25% of the world have NAFLD, which is now one of the leading causes of cirrhosis and indications for liver transplantation. Although liver-related mortality is common, the most common cause of death in patients with NAFLD is related to cardiovascular diseases, followed by extra-hepatic cancers. There is a significant interindividual variability in the susceptibility to liver disease. The severity of metabolic alterations is the main risk factor for progressive NAFLD, but the qualitative components of diet, physical activity and genetic factors also play an important role. In particular, common variants in patatin-like phospholipase domain-containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), membrane bound O-acyl transferase 7 (MBOAT7) and glucokinase regulator (GCKR) have been shown to contribute to the full spectrum of NAFLD. In those at risk of a potentially progressive form of NAFLD or non-alcoholic steatohepatitis or in those with hepatic fibrosis, additional assessment must be made.
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Affiliation(s)
- Angelo Armandi
- Department of Medical SciencesDivision of Gastroenterology and HepatologyA.O. Città della Salute e della Scienza di TorinoUniversity of TurinTurinItaly
| | - Elisabetta Bugianesi
- Department of Medical SciencesDivision of Gastroenterology and HepatologyA.O. Città della Salute e della Scienza di TorinoUniversity of TurinTurinItaly
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28
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Chen Z, Liu J, Zhou F, Li H, Zhang XJ, She ZG, Lu Z, Cai J, Li H. Nonalcoholic Fatty Liver Disease: An Emerging Driver of Cardiac Arrhythmia. Circ Res 2021; 128:1747-1765. [PMID: 34043417 DOI: 10.1161/circresaha.121.319059] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Cardiac arrhythmias and the resulting sudden cardiac death are significant cardiovascular complications that continue to impose a heavy burden on patients and society. An emerging body of evidence indicates that nonalcoholic fatty liver disease (NAFLD) is closely associated with the risk of cardiac arrhythmias, independent of other conventional cardiometabolic comorbidities. Although most studies focus on the relationship between NAFLD and atrial fibrillation, associations with ventricular arrhythmias and cardiac conduction defects have also been reported. Mechanistic investigations suggest that a number of NAFLD-related pathophysiological alterations may potentially elicit structural, electrical, and autonomic remodeling in the heart, contributing to arrhythmogenic substrates in the heart. NAFLD is now the most common liver and metabolic disease in the world. However, the upsurge in the prevalence of NAFLD as an emerging risk factor for cardiac arrhythmias has received little attention. In this review, we summarize the clinical evidence and putative pathophysiological mechanisms for the emerging roles of NAFLD in cardiac arrhythmias, with the purpose of highlighting the notion that NAFLD may serve as an independent risk factor and a potential driving force in the development and progression of cardiac arrhythmias.
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Affiliation(s)
- Ze Chen
- Department of Cardiology, Renmin Hospital of Wuhan University, China (Z.C., J.L., H.L., X.-J.Z., Z.-G.S., H.L.)
- Department of Cardiology (Z.C., Z.L.), Zhongnan Hospital of Wuhan University, China
- Institute of Model Animal (Z.C., J.L., F.Z., H.L., X.-J.Z., Z.-G.S., J.C., H.L.), Wuhan University, China
| | - Jiayi Liu
- Department of Cardiology, Renmin Hospital of Wuhan University, China (Z.C., J.L., H.L., X.-J.Z., Z.-G.S., H.L.)
- Institute of Model Animal (Z.C., J.L., F.Z., H.L., X.-J.Z., Z.-G.S., J.C., H.L.), Wuhan University, China
| | - Feng Zhou
- Medical Science Research Center (F.Z., H.L.), Zhongnan Hospital of Wuhan University, China
- Institute of Model Animal (Z.C., J.L., F.Z., H.L., X.-J.Z., Z.-G.S., J.C., H.L.), Wuhan University, China
| | - Haomiao Li
- Department of Cardiology, Renmin Hospital of Wuhan University, China (Z.C., J.L., H.L., X.-J.Z., Z.-G.S., H.L.)
- Medical Science Research Center (F.Z., H.L.), Zhongnan Hospital of Wuhan University, China
- Institute of Model Animal (Z.C., J.L., F.Z., H.L., X.-J.Z., Z.-G.S., J.C., H.L.), Wuhan University, China
| | - Xiao-Jing Zhang
- Department of Cardiology, Renmin Hospital of Wuhan University, China (Z.C., J.L., H.L., X.-J.Z., Z.-G.S., H.L.)
- Institute of Model Animal (Z.C., J.L., F.Z., H.L., X.-J.Z., Z.-G.S., J.C., H.L.), Wuhan University, China
| | - Zhi-Gang She
- Department of Cardiology, Renmin Hospital of Wuhan University, China (Z.C., J.L., H.L., X.-J.Z., Z.-G.S., H.L.)
- Institute of Model Animal (Z.C., J.L., F.Z., H.L., X.-J.Z., Z.-G.S., J.C., H.L.), Wuhan University, China
| | - Zhibing Lu
- Department of Cardiology (Z.C., Z.L.), Zhongnan Hospital of Wuhan University, China
| | - Jingjing Cai
- Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China (J.C.)
- Institute of Model Animal (Z.C., J.L., F.Z., H.L., X.-J.Z., Z.-G.S., J.C., H.L.), Wuhan University, China
| | - Hongliang Li
- Department of Cardiology, Renmin Hospital of Wuhan University, China (Z.C., J.L., H.L., X.-J.Z., Z.-G.S., H.L.)
- Institute of Model Animal (Z.C., J.L., F.Z., H.L., X.-J.Z., Z.-G.S., J.C., H.L.), Wuhan University, China
- Basic Medical School (H.L.), Wuhan University, China
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Jichitu A, Bungau S, Stanescu AMA, Vesa CM, Toma MM, Bustea C, Iurciuc S, Rus M, Bacalbasa N, Diaconu CC. Non-Alcoholic Fatty Liver Disease and Cardiovascular Comorbidities: Pathophysiological Links, Diagnosis, and Therapeutic Management. Diagnostics (Basel) 2021; 11:689. [PMID: 33921359 PMCID: PMC8069361 DOI: 10.3390/diagnostics11040689] [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: 03/15/2021] [Revised: 04/09/2021] [Accepted: 04/11/2021] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has a growing prevalence in recent years. Its association with cardiovascular disease has been intensively studied, and certain correlations have been identified. The connection between these two entities has lately aroused interest regarding therapeutic management. In order to find the best therapeutic options, a detailed understanding of the pathophysiology that links (NAFLD) to cardiovascular comorbidities is needed. This review focuses on the pathogenic mechanisms that are behind these two diseases and on the therapeutic management available at this time.
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Affiliation(s)
- Alexandra Jichitu
- Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania; (A.J.); (C.C.D.)
| | - Simona Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania;
| | - Ana Maria Alexandra Stanescu
- Department 5, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Cosmin Mihai Vesa
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (C.M.V.); (C.B.)
| | - Mirela Marioara Toma
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania;
| | - Cristiana Bustea
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (C.M.V.); (C.B.)
| | - Stela Iurciuc
- Department of Cardiology, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Marius Rus
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania;
| | - Nicolae Bacalbasa
- Department 13, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Department of Surgery, “Ion Cantacuzino” Clinical Hospital, 030167 Bucharest, Romania
| | - Camelia Cristina Diaconu
- Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania; (A.J.); (C.C.D.)
- Department 5, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
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Abstract
The epidemiology and the current burden of chronic liver disease are changing globally, with non-alcoholic fatty liver disease (NAFLD) becoming the most frequent cause of liver disease in close relationship with the global epidemics of obesity, type 2 diabetes and metabolic syndrome. The clinical phenotypes of NAFLD are very heterogeneous in relationship with multiple pathways involved in the disease progression. In the absence of a specific treatment for non-alcoholic steatohepatitis (NASH), it is important to understand the natural history of the disease, to identify and to optimize the control of factors that are involved in disease progression. In this paper we propose a critical analysis of factors that are involved in the progression of the liver damage and the occurrence of extra-hepatic complications (cardiovascular diseases, extra hepatic cancer) in patients with NAFLD. We also briefly discuss the impact of the heterogeneity of the clinical phenotype of NAFLD on the clinical practice globally and at the individual level.
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Affiliation(s)
- Raluca Pais
- Institut de Cardiométabolisme et Nutrition, Hôpital Pitié Salpetrière, Assistance Publique Hôpitaux de Paris, 75013 Paris, France;
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31
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Role of the sympathetic nervous system in cardiometabolic control: implications for targeted multiorgan neuromodulation approaches. J Hypertens 2021; 39:1478-1489. [PMID: 33657580 DOI: 10.1097/hjh.0000000000002839] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Sympathetic overdrive plays a key role in the perturbation of cardiometabolic homeostasis. Diet-induced and exercise-induced weight loss remains a key strategy to combat metabolic disorders, but is often difficult to achieve. Current pharmacological approaches result in variable responses in different patient cohorts and long-term efficacy may be limited by medication intolerance and nonadherence. A clinical need exists for complementary therapies to curb the burden of cardiometabolic diseases. One such approach may include interventional sympathetic neuromodulation of organs relevant to cardiometabolic control. The experience from catheter-based renal denervation studies clearly demonstrates the feasibility, safety and efficacy of such an approach. In analogy, denervation of the common hepatic artery is now feasible in humans and may prove to be similarly useful in modulating sympathetic overdrive directed towards the liver, pancreas and duodenum. Such a targeted multiorgan neuromodulation strategy may beneficially influence multiple aspects of the cardiometabolic disease continuum offering a holistic approach.
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Gaborit B, Ancel P, Abdullah AE, Maurice F, Abdesselam I, Calen A, Soghomonian A, Houssays M, Varlet I, Eisinger M, Lasbleiz A, Peiretti F, Bornet CE, Lefur Y, Pini L, Rapacchi S, Bernard M, Resseguier N, Darmon P, Kober F, Dutour A. Effect of empagliflozin on ectopic fat stores and myocardial energetics in type 2 diabetes: the EMPACEF study. Cardiovasc Diabetol 2021; 20:57. [PMID: 33648515 PMCID: PMC7919089 DOI: 10.1186/s12933-021-01237-2] [Citation(s) in RCA: 92] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 02/01/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Empagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that has demonstrated cardiovascular and renal protection in patients with type 2 diabetes (T2D). We hypothesized that empaglifozin (EMPA) could modulate ectopic fat stores and myocardial energetics in high-fat-high-sucrose (HFHS) diet mice and in type 2 diabetics (T2D). METHODS C57BL/6 HFHS mice (n = 24) and T2D subjects (n = 56) were randomly assigned to 12 weeks of treatment with EMPA (30 mg/kg in mice, 10 mg/day in humans) or with placebo. A 4.7 T or 3 T MRI with 1H-MRS evaluation-myocardial fat (primary endpoint) and liver fat content (LFC)-were performed at baseline and at 12 weeks. In humans, standard cardiac MRI was coupled with myocardial energetics (PCr/ATP) measured with 31P-MRS. Subcutaneous (SAT) abdominal, visceral (VAT), epicardial and pancreatic fat were also evaluated. The primary efficacy endpoint was the change in epicardial fat volume between EMPA and placebo from baseline to 12 weeks. Secondary endpoints were the differences in PCr/ATP ratio, myocardial, liver and pancreatic fat content, SAT and VAT between groups at 12 weeks. RESULTS In mice fed HFHS, EMPA significantly improved glucose tolerance and increased blood ketone bodies (KB) and β-hydroxybutyrate levels (p < 0.05) compared to placebo. Mice fed HFHS had increased myocardial and liver fat content compared to standard diet mice. EMPA significantly attenuated liver fat content by 55%, (p < 0.001) but had no effect on myocardial fat. In the human study, all the 56 patients had normal LV function with mean LVEF = 63.4 ± 7.9%. Compared to placebo, T2D patients treated with EMPA significantly lost weight (- 2.6 kg [- 1.2; - 3.7]) and improved their HbA1c by 0.88 ± 0.74%. Hematocrit and EPO levels were significantly increased in the EMPA group compared to placebo (p < 0.0001, p = 0.041). EMPA significantly increased glycosuria and plasma KB levels compared to placebo (p < 0.0001, p = 0.012, respectively), and significantly reduced liver fat content (- 27 ± 23 vs. - 2 ± 24%, p = 0.0005) and visceral fat (- 7.8% [- 15.3; - 5.6] vs. - 0.1% [- 1.1;6.5], p = 0.043), but had no effect on myocardial or epicardial fat. At 12 weeks, no significant change was observed in the myocardial PCr/ATP (p = 0.57 between groups). CONCLUSIONS EMPA effectively reduced liver fat in mice and humans without changing epicardial, myocardial fat or myocardial energetics, rebutting the thrifty substrate hypothesis for cardiovascular protection of SGLT2 inhibitors. Trial registration NCT, NCT03118336. Registered 18 April 2017, https://clinicaltrials.gov/ct2/show/NCT03118336.
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Affiliation(s)
- B Gaborit
- Aix Marseille Univ, INSERM, INRAE, C2VN, Marseille, France
- Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle ENDO, APHM, Hôpital Nord, Chemin Des Bourrely, 13915, Marseille cedex 20, France
| | - P Ancel
- Aix Marseille Univ, INSERM, INRAE, C2VN, Marseille, France
| | - A E Abdullah
- Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle ENDO, APHM, Hôpital Nord, Chemin Des Bourrely, 13915, Marseille cedex 20, France
| | - F Maurice
- Aix Marseille Univ, INSERM, INRAE, C2VN, Marseille, France
| | - I Abdesselam
- Aix Marseille Univ, INSERM, INRAE, C2VN, Marseille, France
- Aix Marseille Univ, CNRS, CRMBM, Marseille, France
| | - A Calen
- Aix Marseille Univ, CNRS, CRMBM, Marseille, France
| | - A Soghomonian
- Aix Marseille Univ, INSERM, INRAE, C2VN, Marseille, France
- Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle ENDO, APHM, Hôpital Nord, Chemin Des Bourrely, 13915, Marseille cedex 20, France
| | - M Houssays
- Assistance-Publique Hôpitaux de Marseille, Medical Evaluation Department, CIC-CPCET, 13005, Marseille, France
| | - I Varlet
- Aix Marseille Univ, CNRS, CRMBM, Marseille, France
| | - M Eisinger
- Aix Marseille Univ, INSERM, INRAE, C2VN, Marseille, France
- Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle ENDO, APHM, Hôpital Nord, Chemin Des Bourrely, 13915, Marseille cedex 20, France
| | - A Lasbleiz
- Aix Marseille Univ, INSERM, INRAE, C2VN, Marseille, France
- Aix Marseille Univ, CNRS, CRMBM, Marseille, France
| | - F Peiretti
- Aix Marseille Univ, INSERM, INRAE, C2VN, Marseille, France
| | - C E Bornet
- Support Unit for Clinical Research and Economic Evaluation, Assistance Publique-Hôpitaux de Marseille, 13385, Marseille, France
| | - Y Lefur
- Aix Marseille Univ, CNRS, CRMBM, Marseille, France
| | - L Pini
- Aix Marseille Univ, CNRS, CRMBM, Marseille, France
| | - S Rapacchi
- Aix Marseille Univ, CNRS, CRMBM, Marseille, France
| | - M Bernard
- Aix Marseille Univ, CNRS, CRMBM, Marseille, France
| | - N Resseguier
- Support Unit for Clinical Research and Economic Evaluation, Assistance Publique-Hôpitaux de Marseille, 13385, Marseille, France
- Aix-Marseille Univ, EA 3279 CEReSS-Health Service Research and Quality of Life Center, Marseille, France
| | - P Darmon
- Aix Marseille Univ, INSERM, INRAE, C2VN, Marseille, France
- Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle ENDO, APHM, Hôpital Nord, Chemin Des Bourrely, 13915, Marseille cedex 20, France
| | - F Kober
- Aix Marseille Univ, CNRS, CRMBM, Marseille, France
| | - A Dutour
- Aix Marseille Univ, INSERM, INRAE, C2VN, Marseille, France.
- Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle ENDO, APHM, Hôpital Nord, Chemin Des Bourrely, 13915, Marseille cedex 20, France.
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Fiorentino TV, Miceli S, Succurro E, Sciacqua A, Andreozzi F, Sesti G. Nonalcoholic fatty liver disease is associated with a decreased myocardial mechano-energetic efficiency. J Intern Med 2021; 289:221-231. [PMID: 32633873 DOI: 10.1111/joim.13155] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 06/26/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is linked to a raised risk of cardiovascular diseases (CVD), although the underlying mechanisms are not completely known. A reduced myocardial mechano-energetic efficiency (MEE) has been found to be an independent predictor of CVD. OBJECTIVE To evaluate the association between NAFLD and a compromised MEE. METHODS Myocardial MEE was assessed by a validated echocardiography-derived measure in 699 nondiabetic individuals subdivided into two groups according to ultrasonography defined presence of NAFLD. RESULTS Subjects with NAFLD displayed higher levels of systolic (SBP) and diastolic blood pressure (DBP), triglycerides, fasting and postload glucose, high-sensitivity C-reactive protein (hsCRP), insulin resistance (IR) estimated by HOMA-IR and liver IR index, and lower values of high-density lipoprotein (HDL) in comparison with those without NAFLD. Presence of NAFLD was associated with increased levels of myocardial oxygen demand and reduced values of MEE. MEE was negatively correlated with male sex, age, BMI, waist circumference, SBP, DBP, total cholesterol, triglycerides, fasting and postload glucose, HOMA-IR and liver IR index, hsCRP and positively with HDL levels. In a multivariable regression analysis, presence of NAFLD was associated with MEE regardless of several cardio-metabolic risk factors such as age, gender, waist circumference, SBP, DBP, total and HDL cholesterol, triglycerides, glucose tolerance and hsCRP (β = -0.09, P = 0.04), but not independently of IR estimates. CONCLUSION Ultrasound-defined presence of NAFLD is associated with a decreased MEE, a predictor of adverse cardiovascular events. The relationship between NAFLD and a compromised MEE is dependent of IR.
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Affiliation(s)
- T V Fiorentino
- From the, Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - S Miceli
- From the, Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - E Succurro
- From the, Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - A Sciacqua
- From the, Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - F Andreozzi
- From the, Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - G Sesti
- Department of Clinical and Molecular Medicine, University of Rome-Sapienza, Rome, Italy
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Ledda RE, Milanese G, Cademartiri F, Maffei E, Benedetti G, Goldoni M, Silva M, Sverzellati N. Association of hepatic steatosis with epicardial fat volume and coronary artery disease in symptomatic patients. Radiol Med 2021; 126:652-660. [PMID: 33389661 DOI: 10.1007/s11547-020-01321-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 11/26/2020] [Indexed: 12/12/2022]
Abstract
AIMS This study aims to investigate whether HS-when associated with an excessive amount of epicardial adipose tissue-correlates with CAD in subjects with symptoms suggestive of CVD. METHODS AND RESULTS CCTA images, demographic and clinical variables of 1.182 individuals were retrieved: semi-automated measurements for EFV, CAC, and MLD were obtained. Individuals were grouped into three categories according to the presence of CAD, resulting in absent (CAD0), non-obstructive (CAD1) or obstructive (CAD2) disease-groups, and into two categories based on the presence of HS (with no HS, named HS-, and with HS, named HS+). EFV was significantly higher in HS+ than in HS- group (p < 0.001), whereas MLD was lower in CAD+ than in CAD- subjects (p < 0.001). Two predictive models for CAD were tested: the former included clinical risk factors for CAD along with age, gender, EFV and MLD, whereas the latter did not include clinical variables. The logistic regression analysis of the second proposed model reliably discriminated CAD0 from CAD1 and CAD2 (AUC of 0.712, range 0.682-0.742). CONCLUSION Lower MLD was associated with increased EFV, and MLD-as a marker of HS-discriminate symptomatic patients with CAD from whom without.
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Affiliation(s)
- Roberta Eufrasia Ledda
- Division of Scienze Radiologiche, Department of Medicine and Surgery (DiMeC), University of Parma, Parma, Italy
| | - Gianluca Milanese
- Division of Scienze Radiologiche, Department of Medicine and Surgery (DiMeC), University of Parma, Parma, Italy
| | | | - Erica Maffei
- Department of Radiology, Area Vasta 1/ASUR Marche, Urbino, Italy
| | - Giorgio Benedetti
- Division of Scienze Radiologiche, Department of Medicine and Surgery (DiMeC), University of Parma, Parma, Italy
| | - Matteo Goldoni
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Mario Silva
- Division of Scienze Radiologiche, Department of Medicine and Surgery (DiMeC), University of Parma, Parma, Italy
| | - Nicola Sverzellati
- Division of Scienze Radiologiche, Department of Medicine and Surgery (DiMeC), University of Parma, Parma, Italy.
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Chiu LS, Pedley A, Massaro J, Benjamin EJ, Mitchell GF, McManus DD, Aragam J, Vasan RS, Cheng S, Long MT. The association of non-alcoholic fatty liver disease and cardiac structure and function-Framingham Heart Study. Liver Int 2020; 40:2445-2454. [PMID: 32654390 PMCID: PMC7669676 DOI: 10.1111/liv.14600] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 06/29/2020] [Accepted: 07/01/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Non-alcoholic fatty liver disease confers increased risk for cardiovascular disease, including heart failure (HF), for reasons that remain unclear. Possible pathways could involve an association of liver fat with cardiac structural or functional abnormalities even after accounting for body size. METHODS We analysed N = 2356 Framingham Heart Study participants (age 52 ± 12 years, 52% women) who underwent echocardiography and standardized computed tomography measures of liver fat. RESULTS In cross-sectional multivariable regression models adjusted for age, gender, cohort and cardiovascular risk factors, liver fat was positively associated with left ventricular (LV) mass (β = 1.45; 95% confidence interval (CI): 0.01, 2.88), LV wall thickness (β = 0.01; 95% CI: 0.00, 0.02), mass volume ratio (β = 0.02; 95% CI 0.01, 0.03), mitral peak velocity (E) (β = 0.83; 95% CI 0.31, 1.36) and LV filling pressure (E/e' ratio) (β = 0.16; 95% CI 0.09, 0.23); and inversely associated with global systolic longitudinal strain (β = 0.20, 95% CI 0.07, 0.33), diastolic annular velocity (e') (β = -0.12; 95% CI - 0.22, -0.03), and E/A ratio (β = -0.01; 95% CI - 0.02, -0.00). After additional adjustment for body mass index (BMI), statistical significance was attenuated for all associations except for that of greater liver fat with increased LV filling pressure, a possible precursor to HF (β = 0.11; 95% CI 0.03, 0.18). CONCLUSION Increased liver fat was associated with multiple subclinical cardiac dysfunction measures, with most of associations mediated by obesity. Interestingly, the association of liver fat and LV filling pressure was only partially mediated by BMI, suggesting a possible direct effect of liver fat on LV filling pressure. Further confirmatory studies are needed.
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Affiliation(s)
- Laura S. Chiu
- Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, MA
| | | | - Joseph Massaro
- National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, MA.,Department of Mathematics and Statistics, Boston University, Boston, MA, United States
| | - Emelia J. Benjamin
- National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, MA.,Section of Cardiovascular Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA,Department of Epidemiology, Boston University School of Public Health, Boston, MA
| | | | - David D. McManus
- Cardiology Division, Department of Medicine and the Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worchester, MA
| | - Jayashri Aragam
- Cardiovascular Division, VA Boston Healthcare System, West Roxbury, MA,Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, MA,Harvard Medical School, Boston, MA
| | - Ramachandran S. Vasan
- National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, MA.,Section of Cardiovascular Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA,Department of Epidemiology, Boston University School of Public Health, Boston, MA,Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston Medical Center, Boston, MA
| | - Susan Cheng
- Barbra Streisand Women’s Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Michelle T. Long
- Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, MA
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Prevalence and staging of non-alcoholic fatty liver disease among patients with heart failure with preserved ejection fraction. Sci Rep 2020; 10:12440. [PMID: 32709942 PMCID: PMC7381602 DOI: 10.1038/s41598-020-69013-y] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 07/06/2020] [Indexed: 12/11/2022] Open
Abstract
Insulin resistance and altered energy metabolism is common in non-alcoholic fatty liver disease (NAFLD) and appears to also be associated with myocardial dysfunction. We aimed to evaluate prevalence, staging and clinical features correlated with NAFLD among patients with heart failure with preserved ejection fraction (HFpEF). Adults with HFpEF were prospectively enrolled. Demographic and clinical data were collected. NAFLD was defined based on liver biopsy, abdominal imaging or ICD-coding and the absence of other liver diseases. Descriptive, bivariate and multivariable analyses were performed. 181 patients were analyzed. The median age was 70 with 89% white, 59% female, median BMI 35.1, and 48% with diabetes. NAFLD was present in 27% of the full cohort and 50% of those with imaging. In patients with imaging, multivariable analysis identified diabetes (OR 3.38, 95% CI 1.29–8.88) and BMI (OR 1.11, 95% CI 1.04–1.19) as independent correlates of NAFLD. 54% of NAFLD patients had a NAFLD fibrosis score consistent with advanced fibrosis. Cirrhosis was present in 6.6% of patients overall and 11.5% with imaging. NAFLD patients had a higher frequency of advanced heart failure (75% vs 55%, p 0.01). NAFLD has a two-fold higher prevalence in HFpEF compared to the general population and is independently associated with BMI and diabetes. Patients with HFpEF and NAFLD also appeared to have more advanced fibrosis including cirrhosis suggesting a potential synergistic effect of cardiac dysfunction on fibrosis risk in NAFLD. This data supports consideration for evaluation of underlying liver disease in HFpEF patients.
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Yu SH. Letter: Association between Non-Alcoholic Steatohepatitis and Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus (Diabetes Metab J 2020;44:267-76). Diabetes Metab J 2020; 44:482-483. [PMID: 32613780 PMCID: PMC7332328 DOI: 10.4093/dmj.2020.0123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Affiliation(s)
- Sung Hoon Yu
- Department of Endocrinology and Metabolism, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea.
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Hu L, Shao X, Qiu C, Shao X, Wang X, Niu R, Wang Y. Hepatic steatosis is associated with abnormal hepatic enzymes, visceral adiposity, altered myocardial glucose uptake measured by 18F-FDG PET/CT. BMC Endocr Disord 2020; 20:75. [PMID: 32460891 PMCID: PMC7254706 DOI: 10.1186/s12902-020-00556-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Accepted: 05/21/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease that affects the liver and a variety of extra-hepatic organ systems. This study aimed to investigate the relationship between hepatic steatosis and glucose metabolism in liver and extra-hepatic tissues and organs. METHODS The whole body 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) images of 191 asymptomatic tumor screening patients were retrospectively analyzed. Patients with the ratio of spleen/liver CT densities > 1.1 were defined to have NAFLD, and their clinical symptoms, laboratory markers, FDG uptake in a variety of tissues and organs including heart, mediastinal blood pool, liver, spleen, pancreas, and skeletal muscle, as well as abdominal adipose tissue volumes including visceral adipose tissue (VAT) volume and subcutaneous adipose tissue (SAT) volume were compared with those of the non-NAFLD patients and used to analyze the independent correlation factors of NAFLD. RESULTS Among the 191 patients, 33 (17.3%) were NAFLD, and 158 (82.7%) were non-NAFLD. There was no significant correlation between the mean standardized uptake value (SUVmean) and CT density of liver as well as the ratio of spleen/liver CT densities. Hepatic steatosis, but not FDG intake, was more significant in NAFLD patients with abnormal liver function than those with normal liver function. Compared with the non-NAFLD patients, NAFLD patients had significantly reduced myocardial glucose metabolism, but significantly increased mediastinal blood pool, spleen SUVmean and abdominal adipose tissue volumes (including VAT and SAT volumes) (P < 0.05). Multivariate regression analysis showed that elevated serum ALT, increased abdominal VAT volume, and decreased myocardial FDG uptake were independent correlation factors for NAFLD. Further studies showed that hepatic steatosis and myocardial FDG uptake were mildly linearly correlated (r = 0.366 with hepatic CT density and - 0.236 with the ratio of spleen/liver CT densities, P < 0.05). CONCLUSIONS NAFLD is a systemic disease that can lead to the change of glucose metabolism in some extra-hepatic tissues and organs, especially the myocardium.
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Affiliation(s)
- Lijun Hu
- Department of Radiation Oncology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, 213003 Jiangsu China
| | - Xiaoliang Shao
- Department of Nuclear Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, 213003 Jiangsu China
| | - Chun Qiu
- Department of Nuclear Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, 213003 Jiangsu China
| | - Xiaonan Shao
- Department of Nuclear Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, 213003 Jiangsu China
| | - Xiaosong Wang
- Department of Nuclear Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, 213003 Jiangsu China
| | - Rong Niu
- Department of Nuclear Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, 213003 Jiangsu China
| | - Yuetao Wang
- Department of Nuclear Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, 213003 Jiangsu China
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Abstract
This review addresses the interplay between obesity, type 2 diabetes mellitus, and cardiovascular diseases. It is proposed that obesity, generally defined by an excess of body fat causing prejudice to health, can no longer be evaluated solely by the body mass index (expressed in kg/m2) because it represents a heterogeneous entity. For instance, several cardiometabolic imaging studies have shown that some individuals who have a normal weight or who are overweight are at high risk if they have an excess of visceral adipose tissue-a condition often accompanied by accumulation of fat in normally lean tissues (ectopic fat deposition in liver, heart, skeletal muscle, etc). On the other hand, individuals who are overweight or obese can nevertheless be at much lower risk than expected when faced with excess energy intake if they have the ability to expand their subcutaneous adipose tissue mass, particularly in the gluteal-femoral area. Hence, excessive amounts of visceral adipose tissue and of ectopic fat largely define the cardiovascular disease risk of overweight and moderate obesity. There is also a rapidly expanding subgroup of patients characterized by a high accumulation of body fat (severe obesity). Severe obesity is characterized by specific additional cardiovascular health issues that should receive attention. Because of the difficulties of normalizing body fat content in patients with severe obesity, more aggressive treatments have been studied in this subgroup of individuals such as obesity surgery, also referred to as metabolic surgery. On the basis of the above, we propose that we should refer to obesities rather than obesity.
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Affiliation(s)
- Marie-Eve Piché
- From the Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval (M.-E.P., A.T., J.-P.D.), Université Laval, Québec, QC, Canada.,Department of Medicine, Faculty of Medicine (M.-E.P.), Université Laval, Québec, QC, Canada
| | - André Tchernof
- From the Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval (M.-E.P., A.T., J.-P.D.), Université Laval, Québec, QC, Canada.,School of Nutrition (A.T.), Université Laval, Québec, QC, Canada
| | - Jean-Pierre Després
- From the Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval (M.-E.P., A.T., J.-P.D.), Université Laval, Québec, QC, Canada.,Vitam - Centre de recherche en santé durable, CIUSSS - Capitale-Nationale (J.-P.D.), Université Laval, Québec, QC, Canada.,Department of Kinesiology, Faculty of Medicine (J.-P.D.), Université Laval, Québec, QC, Canada
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Lee H, Kim G, Choi YJ, Huh BW, Lee BW, Kang ES, Cha BS, Lee EJ, Lee YH, Huh KB. Association between Non-Alcoholic Steatohepatitis and Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus. Diabetes Metab J 2020; 44:267-276. [PMID: 30877708 PMCID: PMC7188976 DOI: 10.4093/dmj.2019.0001] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Accepted: 01/16/2019] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Impaired diastolic heart function has been observed in persons with non-alcoholic fatty liver disease (NAFLD) and/or with type 2 diabetes mellitus (T2DM). However, it is unclear whether NAFLD fibrotic progression, i.e., non-alcoholic steatohepatitis, poses an independent risk for diastolic dysfunction in T2DM. We investigated the association between liver fibrosis and left ventricular (LV) diastolic dysfunction in T2DM. METHODS We analyzed 606 patients with T2DM, aged ≥50 years, who had undergone liver ultrasonography and pulsed-wave Doppler echocardiography. Insulin sensitivity was measured by short insulin tolerance test. Presence of NAFLD and/or advanced liver fibrosis was determined by abdominal ultrasonography and NAFLD fibrosis score (NFS). LV diastolic dysfunction was defined according to transmitral peak early to late ventricular filling (E/A) ratio and deceleration time, using echocardiography. RESULTS LV diastolic dysfunction was significantly more prevalent in the NAFLD versus non-NAFLD group (59.7% vs. 49.0%, P=0.011). When NAFLD was stratified by NFS, subjects with advanced liver fibrosis exhibited a higher prevalence of diastolic dysfunction (49.0%, 50.7%, 61.8%; none, simple steatosis, advanced fibrosis, respectively; P for trend=0.003). In multivariable logistic regression, liver fibrosis was independently associated with diastolic dysfunction (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.07 to 2.34; P=0.022) after adjusting for insulin resistance and cardiometabolic risk factors. This association remained significant in patients without insulin resistance (OR, 4.32; 95% CI, 1.73 to 11.51; P=0.002). CONCLUSIONS Liver fibrosis was associated with LV diastolic dysfunction in patients with T2DM and may be an independent risk factor for diastolic dysfunction, especially in patients without systemic insulin resistance.
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Affiliation(s)
- Hokyou Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Gyuri Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young Ju Choi
- Huh's Diabetes Center and the 21st Century Diabetes and Vascular Research Institute, Seoul, Korea
| | - Byung Wook Huh
- Huh's Diabetes Center and the 21st Century Diabetes and Vascular Research Institute, Seoul, Korea
| | - Byung Wan Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
| | - Eun Seok Kang
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Bong Soo Cha
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Eun Jig Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Yong Ho Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
- Department of Systems Biology, Glycosylation Network Research Center, Yonsei University, Seoul, Korea.
| | - Kap Bum Huh
- Huh's Diabetes Center and the 21st Century Diabetes and Vascular Research Institute, Seoul, Korea
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Wattacheril J. Extrahepatic Manifestations of Nonalcoholic Fatty Liver Disease. Gastroenterol Clin North Am 2020; 49:141-149. [PMID: 32033760 DOI: 10.1016/j.gtc.2019.10.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) represents a global public health burden. NAFLD, while strongly associated with the metabolic syndrome, can occur independently from existing metabolic diseases. In addition to liver-related disease burden and mortality, significant extrahepatic disease outcomes coexist with NAFLD, including cardiovascular diseases, chronic kidney disease, and type 2 diabetes. Management of these comorbidities contributes to the overall public health burden of NAFLD. These extrahepatic manifestations require healthcare interventions that are vigilant in monitoring for progression of liver disease while simultaneously managing overall morbidity and mortality from other organ systems.
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Affiliation(s)
- Julia Wattacheril
- Center for Liver Disease and Transplantation, Columbia University Irving Medical Center - NY Presbyterian Hospital, 622 West 168th Street, PH 14-105D, New York, NY 10032, USA.
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Cai J, Zhang XJ, Ji YX, Zhang P, She ZG, Li H. Nonalcoholic Fatty Liver Disease Pandemic Fuels the Upsurge in Cardiovascular Diseases. Circ Res 2020; 126:679-704. [PMID: 32105577 DOI: 10.1161/circresaha.119.316337] [Citation(s) in RCA: 125] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Cardiovascular diseases (CVDs) remain a leading cause of death worldwide. Among the major risk factors for CVD, obesity and diabetes mellitus have received considerable attention in terms of public policy and awareness. However, the emerging prevalence of nonalcoholic fatty liver disease (NAFLD), as the most common liver and metabolic disease and a cause of CVD, has been largely overlooked. Currently, the number of individuals with NAFLD is greater than the total number of individuals with diabetes mellitus and obesity. Epidemiological studies have established a strong correlation between NAFLD and an increased risk of CVD and CVD-associated events. Although debate continues over the causal relationship between NAFLD and CVD, many mechanistic and longitudinal studies have indicated that NAFLD is one of the major driving forces for CVD and should be recognized as an independent risk factor for CVD apart from other metabolic disorders. In this review, we summarize the clinical evidence that supports NAFLD as a risk factor for CVD epidemics and discuss major mechanistic insights regarding the acceleration of CVD in the setting of NAFLD. Finally, we address the potential treatments for NAFLD and their potential impact on CVD.
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Affiliation(s)
- Jingjing Cai
- Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China (J.C.)
- Institute of Model Animal of Wuhan University, China (J.C., X.-J.Z., Y.-X.J., P.Z., Z.-G.S., H.L.)
| | - Xiao-Jing Zhang
- From the Department of Cardiology, Renmin Hospital of Wuhan University, China (X.-J.Z., P.Z., Z.-G.S., H.L.)
- Institute of Model Animal of Wuhan University, China (J.C., X.-J.Z., Y.-X.J., P.Z., Z.-G.S., H.L.)
- Medical Science Research Center, Zhongnan Hospital of Wuhan University, China (X.-J.Z.)
| | - Yan-Xiao Ji
- Institute of Model Animal of Wuhan University, China (J.C., X.-J.Z., Y.-X.J., P.Z., Z.-G.S., H.L.)
| | - Peng Zhang
- From the Department of Cardiology, Renmin Hospital of Wuhan University, China (X.-J.Z., P.Z., Z.-G.S., H.L.)
- Institute of Model Animal of Wuhan University, China (J.C., X.-J.Z., Y.-X.J., P.Z., Z.-G.S., H.L.)
| | - Zhi-Gang She
- From the Department of Cardiology, Renmin Hospital of Wuhan University, China (X.-J.Z., P.Z., Z.-G.S., H.L.)
- Institute of Model Animal of Wuhan University, China (J.C., X.-J.Z., Y.-X.J., P.Z., Z.-G.S., H.L.)
| | - Hongliang Li
- From the Department of Cardiology, Renmin Hospital of Wuhan University, China (X.-J.Z., P.Z., Z.-G.S., H.L.)
- Institute of Model Animal of Wuhan University, China (J.C., X.-J.Z., Y.-X.J., P.Z., Z.-G.S., H.L.)
- Basic Medical School, Wuhan University, China (H.L.)
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Lee Y, Lai HTM, de Oliveira Otto MC, Lemaitre RN, McKnight B, King IB, Song X, Huggins GS, Vest AR, Siscovick DS, Mozaffarian D. Serial Biomarkers of De Novo Lipogenesis Fatty Acids and Incident Heart Failure in Older Adults: The Cardiovascular Health Study. J Am Heart Assoc 2020; 9:e014119. [PMID: 32020839 PMCID: PMC7070205 DOI: 10.1161/jaha.119.014119] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 12/06/2019] [Indexed: 12/14/2022]
Abstract
Background De novo lipogenesis (DNL) is an endogenous pathway that converts excess dietary starch, sugar, protein, and alcohol into specific fatty acids (FAs). Although elevated DNL is linked to several metabolic abnormalities, little is known about how long-term habitual levels and changes in levels of FAs in the DNL pathway relate to incident heart failure (HF). Methods and Results We investigated whether habitual levels and changes in serial measures of FAs in the DNL pathway were associated with incident HF among 4249 participants free of HF at baseline. Plasma phospholipid FAs were measured at baseline, 6 years, and 13 years using gas chromatography, and risk factors for HF were measured using standardized methods. Incident HF was centrally adjudicated using medical records. We prospectively evaluated associations with HF risk of (1) habitual FA levels, using cumulative updating to assess long-term exposure, and (2) changes in FA levels over time. During 22.1 years of follow-up, 1304 HF cases occurred. After multivariable adjustment, habitual levels and changes in levels of palmitic acid (16:0) were positively associated with incident HF (interquintile hazard ratio [95% CI]=1.17 [1.00-1.36] and 1.26 [1.03-1.55], respectively). Changes in levels of 7-hexadecenoic acid (16:1n-9) and vaccenic acid (18:1n-7) were each positively associated with risk of HF (1.36 [1.13-1.62], and 1.43 [1.18-1.72], respectively). Habitual levels and changes in levels of myristic acid (14:0), palmitoleic acid (16:1n-7), stearic acid (18:0), and oleic acid (18:1n-9) were not associated with incident HF. Conclusions Both habitual levels and changes in levels of 16:0 were positively associated with incident HF in older adults. Changes in 16:1n-9 and 18:1n-7 were also positively associated with incident HF. These findings support a potential role of DNL or these DNL-related FAs in the development of HF.
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Affiliation(s)
- Yujin Lee
- Friedman School of Nutrition Science and PolicyTufts UniversityBostonMA
| | - Heidi T. M. Lai
- Friedman School of Nutrition Science and PolicyTufts UniversityBostonMA
| | - Marcia C. de Oliveira Otto
- Division of EpidemiologyHuman Genetics and Environmental SciencesThe University of Texas Health Science Center at Houston (UTHealth) School of Public HealthHoustonTX
| | - Rozenn N. Lemaitre
- Cardivascular Health Research UnitDepartment of MedicineUniversity of WashingtonSeattleWA
| | | | - Irena B. King
- Department of Internal MedicineUniversity of New MexicoAlbuquerqueNM
| | | | - Gordon S. Huggins
- Molecular Cardiology Research Institute Center for Translational GenomicsTufts Medical CenterBostonMA
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Mari A, Khoury T, Said Ahmad H, Abu Baker F, Kadah A, Sbeit W, Pellicano R, Mahamid M. The association between non-alcoholic fatty liver disease and valvular heart disease. Minerva Cardioangiol 2020; 68:42-46. [PMID: 31789009 DOI: 10.23736/s0026-4725.19.05087-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Non-alcoholic fatty liver (NAFLD) disease has become the commonest cause of end-stage liver disease. Patients with NAFLD have an increased risk of associated extrahepatic conditions, including structural and functional cardiovascular disease. Still, it is unknown if there is an association between NAFLD and valvular heart disease (VHD). The aim of this paper was to determine the association between NAFLD and VHD. METHODS We performed a single center retrospective study in EMMS Nazareth Hospital from April 2010 to April 2018. All patients who were diagnosed with NAFLD and who had an echocardiography performed within one year were included. Subjects age and sex-matched, who had echocardiography performed in the same period were included in the control group. RESULTS The mean age of the NAFLD group was 41.5±11.7 vs. 42.8±10.8 years of the control group (P=0.2). The prevalence of aortic stenosis, aortic insufficiency, mitral stenosis and mitral insufficiency were significantly higher in NAFLD patients compared to the control group (1.2% vs. 0.22%, 1.32% vs. 0.32%, 0.66% vs. 0.27%, and 1.87% vs. 0.41%, respectively; P<0.001). In the multivariate logistic regression analysis, NAFLD was found to be independent risk factor for VHD (OR 2.39, 95% CI 2.17-2.78, P<0.001). CONCLUSIONS VHD was significantly seen more frequently in NAFLD patients compared to controls. Prospective studies are needed to validate our findings and to elucidate the pathogenesis of VHD in patients with NAFLD.
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Affiliation(s)
- Amir Mari
- Unit of Gastroenterology and Endoscopy, The Nazareth Hospital, EMMS, Nazareth, Israel -
- Faculty of Medicine, Bar-Ilan University, Safed, Israel -
| | - Tawfik Khoury
- Unit of Gastroenterology and Endoscopy, The Nazareth Hospital, EMMS, Nazareth, Israel
- Faculty of Medicine, Bar-Ilan University, Safed, Israel
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
| | - Helal Said Ahmad
- Unit of Gastroenterology and Endoscopy, The Nazareth Hospital, EMMS, Nazareth, Israel
- Faculty of Medicine, Bar-Ilan University, Safed, Israel
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
| | - Fadi Abu Baker
- Department of Gastroenterology and Hepatology, Hillel Yaffe Medical Center, Hadera, Israel
- Technion Faculty of Medicine, Haifa, Israel
| | - Anas Kadah
- Faculty of Medicine, Bar-Ilan University, Safed, Israel
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
| | - Wisam Sbeit
- Faculty of Medicine, Bar-Ilan University, Safed, Israel
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
| | - Rinaldo Pellicano
- Unit of Gastroenterology, Molinette Hospital, Città della Salute e della Scienza, Turin, Italy
| | - Mahmud Mahamid
- Unit of Gastroenterology and Endoscopy, The Nazareth Hospital, EMMS, Nazareth, Israel
- Faculty of Medicine, Bar-Ilan University, Safed, Israel
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Ferrara D, Montecucco F, Dallegri F, Carbone F. Impact of different ectopic fat depots on cardiovascular and metabolic diseases. J Cell Physiol 2019; 234:21630-21641. [PMID: 31106419 DOI: 10.1002/jcp.28821] [Citation(s) in RCA: 129] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 04/17/2019] [Accepted: 04/29/2019] [Indexed: 12/11/2022]
Abstract
A growing body of evidence is pointing out the pathophysiological role of fat accumulation in different organs. Ectopic fat depots within heart, liver, skeletal muscle, kidney, and pancreas as well as around blood vessels might be more associated to cardiometabolic risk than classical variables, such as body mass index. Among different mechanisms, lipid metabolism appears to be particularly influenced by ectopic fat depots. Indeed, intracellular accumulation of nonesterified fatty acids, and triglycerides promotes endoplasmic reticulum stress, mitochondrial uncoupling, oxidative stress, and altered membrane composition/function, finally promoting inflammatory response and cell death. The dysfunctional adipose tissue was shown to induce both local and systemic effects, with relevant clinical consequences. Epicardial fat and myocardial steatosis have been associated with the development of atrial fibrillation and ventricular dysfunction. Similarly perivascular adipose tissue appears to trigger atherosclerosis and hypertension. Nonalcoholic fatty liver disease has been recognized both as the hepatic manifestation of metabolic syndrome and as a cardiovascular (CV) risk factor. Importantly, the renal sinus fat emerged as a potential player in kidney dysfunction. Finally, both skeletal muscle and pancreatic fat depots have been indicated as potential endocrine modulators of insulin resistance. Considering the global rise in the prevalence of obesity, the understanding of mechanisms underlying ectopic fat accumulation represents an urgent need, with potential clinical implications for CV risk stratification. Here, we attempt to update the current knowledge of the different ectopic fat depots, focusing on underlying mechanisms and potential clinical implications.
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Affiliation(s)
- Daniele Ferrara
- Department of Internal Medicine, First Clinic of Internal Medicine, University of Genoa, Genoa, Italy
| | - Fabrizio Montecucco
- Centre of Excellence for Biomedical Research (CEBR), Department of Internal Medicine, First Clinic of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino Genoa-Italian Cardiovascular Network, Genoa, Italy
| | - Franco Dallegri
- Department of Internal Medicine, First Clinic of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino Genoa-Italian Cardiovascular Network, Genoa, Italy
| | - Federico Carbone
- Department of Internal Medicine, First Clinic of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino Genoa-Italian Cardiovascular Network, Genoa, Italy
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Epicardial Adipose Tissue: Clinical Biomarker of Cardio-Metabolic Risk. Int J Mol Sci 2019; 20:ijms20235989. [PMID: 31795098 PMCID: PMC6929015 DOI: 10.3390/ijms20235989] [Citation(s) in RCA: 118] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 11/23/2019] [Accepted: 11/26/2019] [Indexed: 02/07/2023] Open
Abstract
Epicardial adipose tissue (EAT) is part of the visceral adipose tissue (VAT) that surrounds the heart and it is a quantifiable, modifiable, and multifaceted tissue that has both local and systemic effects. When EAT is enlarged, EAT contributes to atherosclerotic cardiovascular disease (ASCVD) risk and plays a role in the development of metabolic syndrome (MetS). In this review, we will discuss the role of EAT in various facets of MetS, including type 2 diabetes mellitus (T2DM) and insulin resistance. We examine the association between EAT and liver steatosis. We also address the correlations of EAT with HIV therapy and with psoriasis. We discuss racial differences in baseline EAT thickness. We conclude that EAT measurement serves as a powerful potential diagnostic tool in assessing cardiovascular and metabolic risk. Measurement of EAT is made less costly, more convenient, and yet accurate and reliable by transthoracic echocardiography. Furthermore, modification of EAT thickness has therapeutic implications for ASCVD, T2DM, and MetS.
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Dong Y, Li G. Cardiac abnormalities in patients with nonalcoholic fatty liver disease : Insights from auxiliary examinations. Herz 2019; 46:158-163. [PMID: 31538216 DOI: 10.1007/s00059-019-04855-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 08/19/2019] [Accepted: 08/26/2019] [Indexed: 12/16/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease in developed countries and is associated with type 2 diabetes mellitus, obesity, hypertension, dyslipidemia, and metabolic syndrome. It is defined as steatosis in over 5% of hepatocytes. The disease spectrum of NAFLD ranges from simple fatty liver to nonalcoholic steatohepatitis, liver fibrosis, even hepatic cirrhosis. The disease affects various extra-hepatic systems such as the cardiovascular system and urinary system. Heart-related disease is identified as the leading cause of mortality in NAFLD patients rather than liver-related disease. In this review, we summarize the cardiac abnormalities (structural, functional, arrhythmic cardiac complications etc.) seen in NAFLD patients with the assistance of auxiliary examinations, such as electrocardiography, echocardiography, computed tomography, magnetic resonance imaging etc. In addition, the epidemiology of NAFLD and how NAFLD affects the myocardium are also discussed.
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Affiliation(s)
- Yu Dong
- Department of Ultrasound, the Second Affiliated Hospital, Dalian Medical University, 116027, Dalian, China
| | - Guangsen Li
- Department of Ultrasound, the Second Affiliated Hospital, Dalian Medical University, 116027, Dalian, China.
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De Cobelli F, Rossini A, Esposito A, Canu T, Manzoni G, Del Maschio A, Rubinacci A, Sirtori M, Losa M, Lanzi R, Perseghin G. Short-term evaluation of cardiac morphology, function, metabolism and structure following diagnosis of adult-onset growth hormone deficiency. Growth Horm IGF Res 2019; 46-47:50-54. [PMID: 31276905 DOI: 10.1016/j.ghir.2019.06.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Revised: 06/03/2019] [Accepted: 06/24/2019] [Indexed: 01/26/2023]
Abstract
OBJECTIVE The impact of growth hormone (GH) deficiency of the adult on cardiovascular function remains only partially elucidated. Purpose of this study was to test cardiac function in adult GH deficient patients using cardiac magnetic resonance (CMR). DESIGN Cardiac magnetic resonance (CMR) techniques, including cardiac 31P MR spectroscopy and evaluation of gadolinium late-enhancement, were applied to assess simultaneously, in a cross-sectional fashion, morphological, functional, metabolic, and structural parameters of the left (LV) and right ventricle (RV) in 15 patients with adult onset GH deficiency. Fifteen healthy individuals served as controls. RESULTS In GH deficient patients LV systolic function (EF%: 61 ± 1.7 vs 62.1 ± 0.8; p = .44) was not different in spite of a lower LV mass (83.2 ± 5.3 vs 145.3 ± 11.9 g; p = .001), a subclinical impairment of diastolic function (E/A peak ratio: 1.6 ± 0.2 vs 2.1 ± 0.2 p = .05), and a trend for lower PCr/ATP ratio (2.1 ± 0.8 vs 2.3 ± 0.1 p = .07). The RV showed reduced chamber size (end diastolic volume 123.8 ± 9 vs 147.9 ± 7.6 mL; p = .021) with preserved mass. No structural alterations of the LV and RV at late-enhancement were detected in these patients. CONCLUSIONS GH deficient patients represent a unique model of reduced LV myocardial mass in which major structural and metabolic alterations are lacking. Mal-adaptive mechanisms developing in the long term in response to GH deficiency and more severely affecting the LV remain to be elucidated.
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Affiliation(s)
- Francesco De Cobelli
- Department of Radiology and Center for Experimental Imaging, San Raffaele Scientific Institute, Milano, Italy; Vita-Salute University, Milano, Italy
| | - Alessandro Rossini
- Endocrinology and Diabetes Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
| | - Antonio Esposito
- Department of Radiology and Center for Experimental Imaging, San Raffaele Scientific Institute, Milano, Italy; Vita-Salute University, Milano, Italy
| | - Tamara Canu
- Department of Radiology and Center for Experimental Imaging, San Raffaele Scientific Institute, Milano, Italy
| | - Giuseppina Manzoni
- Department of Medicine and Rehabilitation, Unit of Metabolic Medicine, Policlinico di Monza, Monza, Italy
| | - Alessandro Del Maschio
- Department of Radiology and Center for Experimental Imaging, San Raffaele Scientific Institute, Milano, Italy; Vita-Salute University, Milano, Italy
| | | | - Marcella Sirtori
- Bone Metabolic Unit, San Raffaele Scientific Institute, Milano, Italy
| | - Marco Losa
- Department of Neurosurgery, San Raffaele Scientific Institute, Milano, Italy
| | - Roberto Lanzi
- Unit of Endocrinology, San Raffaele Scientific Institute, Milano, Italy
| | - Gianluca Perseghin
- Department of Medicine and Rehabilitation, Unit of Metabolic Medicine, Policlinico di Monza, Monza, Italy; Department of Medicine and Surgery, Università degli Studi di Milano Bicocca, Milan, Italy
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Fasting Whole-Body Energy Homeostasis and Hepatic Energy Metabolism in Nondiabetic Humans with Fatty Liver. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:9796175. [PMID: 31097978 PMCID: PMC6487077 DOI: 10.1155/2019/9796175] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Revised: 08/27/2018] [Accepted: 03/18/2019] [Indexed: 01/17/2023]
Abstract
Background Fatty liver is believed to be sustained by a higher than normal adipose-derived NEFA flux to the liver. Also, hepatic energy metabolism may be a rate-limiting step of intrahepatic fat (IHF) accumulation. Aims To assess whole-body energy metabolism and hepatic high-energy phosphates (HEPs) in individuals with fatty liver. Methods We studied 22 individuals with fatty liver and 22 control individuals matched for anthropometric features by means of (1) hepatic 1H-magnetic resonance spectroscopy (MRS) to measure the IHF content, (2) hepatic 31P-MRS to assess the relative content of HEPs (phosphomonoesters, phosphodiesters, inorganic phosphorus, and ATP), and (3) indirect calorimetry to assess whole-body resting energy expenditure and substrate oxidation. Results Patients with newly diagnosed fatty liver and controls were not different for anthropometric parameters. Based on HOMA2%-S, individuals with fatty liver were more insulin resistant than controls. Resting energy expenditure and the pattern of substrate oxidation were not different between groups. Relative content of HEPs was not different between groups; in particular, the Pi/γ-ATP ratio, the most important signals in terms of monitoring energy homeostasis, was not different even if it was associated with indirect calorimetry-derived parameters of oxidative substrate disposal. Conclusions These data demonstrate that fasting whole-body energy metabolism and the relative content of HEPs in nondiabetic patients with fatty liver are not different than those in controls when they are matched for anthropometric features.
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Canada JM, Abbate A, Collen R, Billingsley H, Buckley LF, Carbone S, Trankle CR, Idowu MO, Kadariya D, Van Tassell B, Sanyal AJ, Siddiqui MS. Relation of Hepatic Fibrosis in Nonalcoholic Fatty Liver Disease to Left Ventricular Diastolic Function and Exercise Tolerance. Am J Cardiol 2019; 123:466-473. [PMID: 30502049 PMCID: PMC6331258 DOI: 10.1016/j.amjcard.2018.10.027] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2018] [Revised: 10/26/2018] [Accepted: 10/29/2018] [Indexed: 01/04/2023]
Abstract
The purpose of this study was to determine the relation between liver histology, exercise tolerance, and diastolic function in patients with nonalcoholic fatty liver disease (NAFLD). Myocardial remodeling and diastolic dysfunction have been associated with NAFLD. However, its physiological impact and relationship to the histological severity of NAFLD is not known. Cardiopulmonary exercise testing and stress echocardiography was performed in subjects with biopsy-confirmed NAFLD. Maximal aerobic exercise capacity (peak oxygen consumption [VO2]) was related to diastolic function (mitral annulus Doppler velocity e' and ratio of early diastolic filling pressure [E] to e' [E/e']) at rest and peak exercise. Autonomic dysfunction was determined from heart rate recovery after exercise. Independent predictors of cardiac function and exercise capacity were identified by multivariable regression. Thirty-six subjects (nonalcoholic fatty liver [NAFL = 15], nonalcoholic steatohepatitis [NASH = 21]) were enrolled. NASH was associated with impaired exercise capacity compared with NAFL (median peak VO2 17.0 [15.4, 18.9] vs 19.9 [17.4, 26.0], p = 001); pVO2 declined with increasing fibrosis (F0 = 22.5, F1 = 19.9, F2 = 19.0, F3 = 16.6 ml·kg-1·min-1; p = 0.01). Similarly, E/e' during exercise increased progressively with increasing fibrosis (F0 = 5.6, F1 = 6.5, F2 = 8.7, F3 = 9.8; P = 0.02). Finally, heart rate recovery, a marker of autonomic function, was blunted in those with higher fibrosis stages (F0 = 25 [20, 30], F1 = 23 [17.5, 27.0], F2 = 17 [11.8, 21.5], F3 = 11 [8.5, 18.0] beats per minute; p <0.01). Fibrosis was an independent predictor of these functional outcomes. In conclusion, NASH is associated with impaired exercise capacity and diastolic dysfunction compared with NAFL. The severity of impairment is directly related to the severity of fibrosis stage in precirrhotic stages of NAFLD.
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Affiliation(s)
- Justin McNair Canada
- VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia; Department of Kinesiology & Health Sciences, Virginia Commonwealth University, Richmond, Virginia.
| | - Antonio Abbate
- VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia
| | - Rebecca Collen
- Division of Gastroenterology - Hepatology Division, Virginia Commonwealth University, Richmond, Virginia
| | - Hayley Billingsley
- VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia
| | - Leo Francis Buckley
- VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia
| | - Salvatore Carbone
- VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia
| | - Cory Ross Trankle
- VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia
| | - Michael Ola Idowu
- Department of Pathology, Virginia Commonwealth University, Richmond, Virginia
| | - Dinesh Kadariya
- VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia
| | | | - Arun Jayant Sanyal
- Division of Gastroenterology - Hepatology Division, Virginia Commonwealth University, Richmond, Virginia
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology - Hepatology Division, Virginia Commonwealth University, Richmond, Virginia
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