CoChat
Sign Up
Cited by 37Liver Disease Diagnosis and TreatmentDiabetes, Cardiovascular Risks, and LipoproteinsCardiovascular Disease and Adiposity

The Pathophysiological Associations Between Obesity, NAFLD, and Atherosclerotic Cardiovascular Diseases

Open access
Li, Meng, Cui, Man, Li, Guoxia, Liu, Yueqiu, Xu, Yunsheng, Eftekhar, Seyed Parsa, Ala, Moein·2024·Hormone and Metabolic Research
DOI 10.1055/a-2266-1503
Open this paper in CoChat — free accountOpen PDF

Abstract

Obesity, non-alcoholic fatty liver disease (NAFLD), and atherosclerotic cardiovascular diseases are common and growing public health concerns. Previous epidemiological studies unfolded the robust correlation between obesity, NAFLD, and atherosclerotic cardiovascular diseases. Obesity is a well-known risk factor for NAFLD, and both of them can markedly increase the odds of atherosclerotic cardiovascular diseases. On the other hand, significant weight loss achieved by lifestyle modification, bariatric surgery, or medications, such as semaglutide, can concomitantly improve NAFLD and atherosclerotic cardiovascular diseases. Therefore, certain pathophysiological links are involved in the development of NAFLD in obesity, and atherosclerotic cardiovascular diseases in obesity and NAFLD. Moreover, recent studies indicated that simultaneously targeting several mechanisms by tirzepatide and retatrutide leads to greater weight loss and markedly improves the complications of metabolic syndrome. These findings remind the importance of a mechanistic viewpoint for breaking the association between obesity, NAFLD, and atherosclerotic cardiovascular diseases. In this review article, we mainly focus on shared pathophysiological mechanisms, including insulin resistance, dyslipidemia, GLP1 signaling, inflammation, oxidative stress, mitochondrial dysfunction, gut dysbiosis, renin-angiotensin-aldosterone system (RAAS) overactivity, and endothelial dysfunction. Most of these pathophysiological alterations are primarily initiated by obesity. The development of NAFLD further exacerbates these molecular and cellular alterations, leading to atherosclerotic cardiovascular disease development or progression as the final manifestation of molecular perturbation. A better insight into these mechanisms makes it feasible to develop new multi-target approaches to simultaneously unhinge the deleterious chain of events linking obesity and NAFLD to atherosclerotic cardiovascular diseases.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1055/a-2266-1503

Cites

13 of 13 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • BRI enhances the ability to identify abdominal obesity, particularly in individuals with excess visceral fat, providing a more accurate assessment of this condition.

    “This feature enhances the BRI’s ability to identify abdominal obesity, particularly in individuals with excess visceral fat, providing a more accurate assessment of this condition18.”

    From The nonlinear association between body roundness index and infertility in married women (2025) · cites this paper as [18]

    The Insulin resistance section says visceral fat mass and waist circumference correlate with insulin resistance, but it does not discuss BRI or its accuracy in identifying abdominal obesity. Searches for “BRI,” “body roundness index,” and abdominal-obesity assessment found no passage addressing that claim in our copy. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 168

  1. Chooi YC, Ding C, Magkos F. The epidemiology of obesity. Metabolism 2019; 92: 6-10
  2. Yeh TL, Hsu HY, Tsai MC et al. Association between metabolically healthy obesity/overweight and cardiovascular disease risk: a representative cohort study in Taiwan. PloS One 2021; 16: e0246378
  3. Zou B, Yeo YH, Nguyen VH et al. Prevalence, characteristics and mortality outcomes of obese, nonobese and lean NAFLD in the United States, 1999-2016. J Intern Med 2020; 288: 139-151
  4. Paik JM, Kabbara K, Eberly KE et al. Global burden of NAFLD and chronic liver disease among adolescents and young adults. Hepatology (Baltimore. Md) 2022; 75: 1204-1217
  5. Ito T, Ishigami M, Zou B et al. The epidemiology of NAFLD and lean NAFLD in Japan: a meta-analysis with individual and forecasting analysis, 1995-2040. Hepatol Int 2021; 15: 366-379
  6. Ge X, Zheng L, Wang M et al. Prevalence trends in non-alcoholic fatty liver disease at the global, regional and national levels, 1990-2017: a population-based observational study. BMJ Open 2020; 10: e036663
  7. Dai H, Alsalhe TA, Chalghaf N et al. The global burden of disease attributable to high body mass index in 195 countries and territories, 1990-2017: an analysis of the Global Burden of Disease Study. PLoS Med 2020; 17: e1003198
  8. Henson JB, Simon TG, Kaplan A et al. Advanced fibrosis is associated with incident cardiovascular disease in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2020; 51: 728-736
  9. Ye Q, Zou B, Yeo YH et al. Global prevalence, incidence, and outcomes of non-obese or lean non-alcoholic fatty liver disease: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2020; 5: 739-752
  10. Kim Y, Han E, Lee JS et al. Cardiovascular risk is elevated in lean subjects with nonalcoholic fatty liver disease. Gut Liver 2022; 16: 290-299
  11. Volpe S, Lisco G, Fanelli M et al. Once-weekly subcutaneous semaglutide improves fatty liver disease in patients with type 2 diabetes: a 52-week prospective Real-life study. Nutrients 2022; 14: 4673
  12. Sinn DH, Kang D, Cho SJ et al. Weight change and resolution of fatty liver in normal weight individuals with nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2021; 33: e529-e534
  13. Meneses D, Olveira A, Corripio R et al. The benefit of bariatric surgery on histological features of metabolic associated fatty liver disease assessed through noninvasive methods. Obes Surg 2022; 32: 2682-2695
  14. Hartman ML, Sanyal AJ, Loomba R et al. Effects of novel dual GIP and GLP-1 receptor agonist tirzepatide on biomarkers of nonalcoholic steatohepatitis in patients with type 2 diabetes. Diabetes Care 2020; 43: 1352-1355
  15. Jastreboff AM, Aronne LJ, Ahmad NN et al. Tirzepatide once weekly for the treatment of obesity. N Eng. J Med 2022; 387: 205-216
  16. Jastreboff AM, Kaplan LM, Frías JP et al. Triple-hormone-receptor agonist retatrutide for obesity -a phase 2 trial. N Eng. J Med 2023; 389: 514-526
  17. Sargeant JA, Gray LJ, Bodicoat DH et al. The effect of exercise training on intrahepatic triglyceride and hepatic insulin sensitivity: a systematic review and meta-analysis. Obes Rev 2018; 19: 1446-1459
  18. Zhang M, Hu T, Zhang S et al. Associations of different adipose tissue depots with insulin resistance: a systematic review and meta-analysis of observational studies. Sci Rep 2015; 5: 18495
  19. Rao R, Yanagisawa R, Kini S. Insulin resistance and bariatric surgery. Obes Rev 2012; 13: 316-328
  20. Jiao N, Baker SS, Nugent CA et al. Gut microbiome may contribute to insulin resistance and systemic inflammation in obese rodents: a meta-analysis. Physiol Genom 2018; 50: 244-254
  21. Ye J. Mechanisms of insulin resistance in obesity. Front Med 2013; 7: 14-24
  22. Marchesini G, Brizi M, Morselli-Labate AM et al. Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med 1999; 107: 450-455
  23. Lomonaco R, Bril F, Portillo-Sanchez P et al. Metabolic impact of nonalcoholic steatohepatitis in obese patients with type 2 diabetes. Diabetes Care 2016; 39: 632-638
  24. Bugianesi E, Gastaldelli A, Vanni E et al. Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms. Diabetologia 2005; 48: 634-642
  25. Ipsen DH, Lykkesfeldt J, Tveden-Nyborg P. Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease. Cell Mol Life Sci 2018; 75: 3313-3327
  26. Zheng F, Cai Y. Concurrent exercise improves insulin resistance and nonalcoholic fatty liver disease by upregulating PPAR-γ and genes involved in the beta-oxidation of fatty acids in ApoE-KO mice fed a high-fat diet. Lipids Health Dis 2019; 18: 6
  27. Chen Y, Feng R, Yang X et al. Yogurt improves insulin resistance and liver fat in obese women with nonalcoholic fatty liver disease and metabolic syndrome: a randomized controlled trial. Am J Clin Nutr 2019; 109: 1611-1619
  28. Honma M, Sawada S, Ueno Y et al. Selective insulin resistance with differential expressions of IRS-1 and IRS-2 in human NAFLD livers. Int J Obes (Lond) 2018; 42: 1544-1555
  29. Lyu K, Zhang Y, Zhang D et al. A membrane-bound diacylglycerol species induces PKCε-mediated hepatic insulin resistance. Cell Metab 2020; 32: 654-664.e5
  30. Ding X, Wang X, Wu J et al. Triglyceride-glucose index and the incidence of atherosclerotic cardiovascular diseases: a meta-analysis of cohort studies. Cardiovasc Diabetol 2021; 20: 76
  31. Meza CA, La Favor JD, Kim DH et al. Endothelial dysfunction: is there a hyperglycemia-induced imbalance of NOX and NOS? Int J Mol Sci 2019; 20: 3775
  32. Ouwens DM, Boer C, Fodor M et al. Cardiac dysfunction induced by high-fat diet is associated with altered myocardial insulin signalling in rats. Diabetologia 2005; 48: 1229-1237
  33. Erqou S, Adler AI, Challa AA et al. Insulin resistance and incident heart failure: a meta-analysis. Eur J Heart Fail 2022; 24: 1139-1141
  34. Tang N, Ma J, Tao R et al. The effects of the interaction between BMI and dyslipidemia on hypertension in adults. Sci Rep 2022; 12: 927
  35. Murad MH, Hazem A, Coto-Yglesias F et al. The association of hypertriglyceridemia with cardiovascular events and pancreatitis: a systematic review and meta-analysis. BMC Endocr Disord 2012; 12: 2
  36. Mora S, Glynn RJ, Hsia J et al. Statins for the primary prevention of cardiovascular events in women with elevated high-sensitivity C-reactive protein or dyslipidemia: results from the justification for the use of statins in prevention: an intervention trial evaluating rosuvastatin (JUPITER) and meta-analysis of women from primary prevention trials. Circulation 2010; 121: 1069-1077
  37. Chen KN, He L, Zhong LM et al. Meta-analysis of dyslipidemia management for the prevention of ischemic stroke recurrence in China. Front Neurol 2020; 11: 483570
  38. Bril F, Sninsky JJ, Baca AM et al. Hepatic steatosis and insulin resistance, but not steatohepatitis, promote atherogenic dyslipidemia in NAFLD. J Clin Endocrinol Metab 2016; 101: 644-652
  39. Amor AJ, Pinyol M, Solà E et al. Relationship between noninvasive scores of nonalcoholic fatty liver disease and nuclear magnetic resonance lipoprotein abnormalities: a focus on atherogenic dyslipidemia. J Clin Lipidol 2017; 11: 551-561.e557
  40. Dowla S, Aslibekyan S, Goss A et al. Dyslipidemia is associated with pediatric nonalcoholic fatty liver disease. J Clin Lipidol 2018; 12: 981-987
  41. Speliotes EK, Massaro JM, Hoffmann U et al. Fatty liver is associated with dyslipidemia and dysglycemia independent of visceral fat: the Framingham Heart Study. Hepatology 2010; 51: 1979-1987
  42. Hodson L, Gunn PJ. The regulation of hepatic fatty acid synthesis and partitioning: the effect of nutritional state. Nat Rev Endocrinol 2019; 15: 689-700
  43. van Bloemendaal L, Ten Kulve JS, la Fleur SE et al. Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS. J Endocrinol 2014; 221: T1-T16
  44. Yang X, Zhang M, Lu Z et al. Novel small molecule glucagon-like peptide-1 receptor agonist S6 stimulates insulin secretion from rat islets. Front Pharmacol 2021; 12: 664802
  45. Rodrigues T, Borges P, Mar L et al. GLP-1 improves adipose tissue glyoxalase activity and capillarization improving insulin sensitivity in type 2 diabetes. Pharmacol Res 2020; 161: 105198
  46. Lincoff AM, Brown-Frandsen K, Colhoun HM et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Eng J Med 2023; 389: 2221-2232
  47. Bernosky-Smith KA, Stanger DB, Trujillo AJ et al. The GLP-1 agonist exendin-4 attenuates self-administration of sweetened fat on fixed and progressive ratio schedules of reinforcement in rats. Pharmacol Biochem Behav 2016; 142: 48-55
  48. Zhou R, Lin C, Cheng Y et al. Liraglutide alleviates hepatic steatosis and liver injury in T2MD rats via a GLP-1R dependent AMPK pathway. Front Pharmacol 2020; 11: 600175
  49. Gao Z, Song GY, Ren LP et al. β-catenin mediates the effect of GLP-1 receptor agonist on ameliorating hepatic steatosis induced by high fructose diet. Eur J Histochem 2020; 64: 3160
  50. Bandyopadhyay S, Das S, Samajdar SS et al. Role of semaglutide in the treatment of nonalcoholic fatty liver disease or non-alcoholic steatohepatitis: a systematic review and meta-analysis. Diabetes Metab Syndr 2023; 17: 102849
  51. Hagerich K, Durkee M, Goldstein MG. Tirzepatide once weekly for the treatment of obesity. N Eng J Med 2022; 387: 1433
  52. Ajaz S, McPhail MJ, Gnudi L et al. Mitochondrial dysfunction as a mechanistic biomarker in patients with non-alcoholic fatty liver disease (NAFLD). Mitochondrion 2021; 57: 119-130
  53. Zhang X, Zhang J, Sun H et al. Defective phosphatidylglycerol remodeling causes hepatopathy, linking mitochondrial dysfunction to hepatosteatosis. Cell Mol Gastroenterol Hepatol 2019; 7: 763-781
  54. Rector RS, Thyfault JP, Uptergrove GM et al. Mitochondrial dysfunction precedes insulin resistance and hepatic steatosis and contributes to the natural history of non-alcoholic fatty liver disease in an obese rodent model. J Hepatol 2010; 52: 727-736
  55. Chella Krishnan K, Kurt Z, Barrere-Cain R et al. Integration of multi-omics data from mouse diversity panel highlights mitochondrial dysfunction in non-alcoholic fatty liver disease. Cell Syst 2018; 6: 103-115.e107
  56. Yang XX, Wang X, Shi TT et al. Mitochondrial dysfunction in high-fat diet-induced nonalcoholic fatty liver disease: The alleviating effect and its mechanism of Polygonatum kingianum. Biomed Pharmacother 2019; 117: 109083
  57. Ortiz M, Soto-Alarcón SA, Orellana P et al. Suppression of high-fat diet-induced obesity-associated liver mitochondrial dysfunction by docosahexaenoic acid and hydroxytyrosol co-administration. Dig Liver Dis 2020; 52: 895-904
  58. Chistiakov DA, Shkurat TP, Melnichenko AA et al. The role of mitochondrial dysfunction in cardiovascular disease: a brief review. Ann Med 2018; 50: 121-127
  59. Tajes M, Díez-López C, Enjuanes C et al. Neurohormonal activation induces intracellular iron deficiency and mitochondrial dysfunction in cardiac cells. Cell Biosci 2021; 11: 89
  60. Ribeiro Junior RF, Dabkowski ER, Shekar KC et al. MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload. Free Radic Biol Med 2018; 117: 18-29
  61. Glanz VY, Sobenin IA, Grechko AV et al. The role of mitochondria in cardiovascular diseases related to atherosclerosis. Front Biosci (Elite Ed) 2020; 12: 102-112
  62. Guo C, Wang J, Jing L et al. Mitochondrial dysfunction, perturbations of mitochondrial dynamics and biogenesis involved in endothelial injury induced by silica nanoparticles. Environ Pollut 2018; 236: 926-936
  63. Cohen E, Margalit I, Shochat T et al. Markers of chronic inflammation in overweight and obese individuals and the role of gender: a cross- sectional study of a large cohort. J Inflam Res 2021; 14: 567-573
  64. Mărginean CO, Meliţ LE, Huțanu A et al. The adipokines and inflammatory status in the era of pediatric obesity. Cytokine 2020; 126: 154925
  65. Alzamil H. Elevated serum TNF-α is related to obesity in type 2 diabetes mellitus and is associated with glycemic control and insulin resistance. J Obes 2020; 2020: 5076858. doi: 10.1155/2020/5076858. PMID: 32089876; PMCID: PMC7013317 · DOI
  66. Yu E, Hsu H-Y, Huang C-Y et al. Inflammatory biomarkers and risk of atherosclerotic cardiovascular disease. Open Med 2018; 13: 208-213
  67. Lund MAV, Thostrup AH, Frithioff-Bøjsøe C et al. Low-grade inflammation independently associates with cardiometabolic risk in children with overweight/obesity. Nutr Metab Cardiovasc Dis 2020; 30: 1544-1553
  68. Su Z, Efremov L, Mikolajczyk R. Differences in the levels of inflammatory markers between metabolically healthy obese and other obesity phenotypes in adults: a systematic review and meta-analysis. Nutr Metab Cardiovasc Dis; 2023 S0939-4753(23) 00348-4 . DOI: 10.1016/j.numecd.2023.09.002 · DOI
  69. Fuchs A, Samovski D, Smith GI et al. Associations among adipose tissue immunology, inflammation, exosomes and insulin sensitivity in people with obesity and nonalcoholic fatty liver disease. Gastroenterology 2021; 161: 968-981.e912
  70. Duan Y, Pan X, Luo J et al. Association of inflammatory cytokines with non-alcoholic fatty liver disease. Front Immunol 2022; 13: 880298
  71. Al Rifai M, Silverman MG, Nasir K et al. The association of nonalcoholic fatty liver disease, obesity, and metabolic syndrome, with systemic inflammation and subclinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis 2015; 239: 629-633
  72. Gao X, Li Y, Ma Z et al. Obesity induces morphological and functional changes in female reproductive system through increases in NF-κB and MAPK signaling in mice. Reprod Biol Endocrinol 2021; 19: 148
  73. Renovato-Martins M, Moreira-Nunes C, Atella GC et al. Obese adipose tissue secretion induces inflammation in preadipocytes: role of toll-like receptor-4. Nutrients 2020; 12: 2828
  74. Kim EJ, Kim BH, Seo HS et al. Cholesterol-induced non-alcoholic fatty liver disease and atherosclerosis aggravated by systemic inflammation. PloS One 2014; 9: e97841
  75. Ye L, Chen X, Wang M et al. Curcumin analogue C66 attenuates obesity-induced myocardial injury by inhibiting JNK-mediated inflammation. Biomed Pharmacother 2021; 143: 112121
  76. Uddandrao VS, Chandrasekaran P, Saravanan G et al. Phytoformulation with hydroxycitric acid and capsaicin protects against high-fat-diet-induced obesity cardiomyopathy by reducing cardiac lipid deposition and ameliorating inflammation and apoptosis in the heart. J Trad Complement Med 2023; . DOI: 10.1016/j. jtcme.2023.08.004. https://www.sciencedirect.com/science/article/ pii/S2225411023000883 · DOI
  77. Gao S, Xue X, Yin J et al. Danlou tablet inhibits the inflammatory reaction of high-fat diet-induced atherosclerosis in ApoE knockout mice with myocardial ischemia via the NF-κB signaling pathway. J Ethnopharmacol 2020; 263: 113158
  78. Gutiérrez-Cuevas J, Sandoval-Rodríguez A, Monroy-Ramírez HC et al. Prolonged-release pirfenidone prevents obesity-induced cardiac steatosis and fibrosis in a mouse NASH model. Cardiovasc Drugs The 2021; 35: 927-938
  79. Canfora EE, Meex RCR, Venema K et al. Gut microbial metabolites in obesity, NAFLD and T2DM. Nat Rev Endocrinol 2019; 15: 261-273
  80. Yassour M, Lim MY, Yun HS et al. Sub-clinical detection of gut microbial biomarkers of obesity and type 2 diabetes. Genome Med 2016; 8: 176
  81. Monga Kravetz A, Testerman T, Galuppo B et al. Effect of gut microbiota and PNPLA3 rs738409 variant on nonalcoholic fatty liver disease (NAFLD) in obese youth. J Clin Endocrinol Metab 2020; 105: e3575-e3585
  82. Chen YH, Chiu CC, Hung SW et al. Gnotobiotic mice inoculated with Firmicutes, but not Bacteroidetes, deteriorate nonalcoholic fatty liver disease severity by modulating hepatic lipid metabolism. Nutr Res 2019; 69: 20-29
  83. Iino C, Endo T, Mikami K et al. Significant decrease in faecalibacterium among gut microbiota in nonalcoholic fatty liver disease: a large BMI-and sex-matched population study. Hepatol Int 2019; 13: 748-756
  84. Zhang Y, Xu J, Wang X et al. Changes of intestinal bacterial microbiota in coronary heart disease complicated with nonalcoholic fatty liver disease. BMC Genom 2019; 20: 862
  85. de Wouters d'Oplinter A, Rastelli M, Van Hul M et al. Gut microbes participate in food preference alterations during obesity. Gut Microbes 2021; 13: 1959242
  86. Kazankov K, Jørgensen SMD, Thomsen KL et al. The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Nat Rev Gastroenterol Hepatol 2019; 16: 145-159
  87. Vrieze A, Van Nood E, Holleman F et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 2012; 143: 913-916.e917
  88. Beale AL, O'Donnell JA, Nakai ME et al. The gut microbiome of heart failure with preserved ejection fraction. J Am Heart Assoc 2021; 10: e020654
  89. Sun W, Du D, Fu T et al. Alterations of the gut microbiota in patients with severe chronic heart failure. Front Microbiol 2021; 12: 813289
  90. Pakhomov N, Baugh JA. The role of diet-derived short-chain fatty acids in regulating cardiac pressure overload. Am J Physiol Heart Circ Physiol 2021; 320: H475-H486
  91. Zhao M, Zhao L, Xiong X et al. TMAVA, a metabolite of intestinal microbes, is increased in plasma from patients with liver steatosis, inhibits γ-butyrobetaine hydroxylase, and exacerbates fatty liver in mice. Gastroenterology 2020; 158: 2266-2281.e2227
  92. Organ CL, Li Z, Sharp TE 3rd et al. Nonlethal inhibition of gut microbial trimethylamine N-oxide production improves cardiac function and remodeling in a murine model of heart failure. J Am Heart Assoc 2020; 9: e016223
  93. Burz SD, Monnoye M, Philippe C et al. Fecal microbiota transplant from human to mice gives insights into the role of the gut microbiota in non-alcoholic fatty liver disease (NAFLD). Microorganisms 2021; 9: 199
  94. Rodriguez J, Hiel S, Neyrinck AM et al. Discovery of the gut microbial signature driving the efficacy of prebiotic intervention in obese patients. Gut 2020; 69: 1975-1987
  95. Wang P, Li D, Ke W et al. Resveratrol-induced gut microbiota reduces obesity in high-fat diet-fed mice. Int J Obes (Lond) 2020; 44: 213-225
  96. Farin W, Oñate FP, Plassais J et al. Impact of laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy on gut microbiota: a metagenomic comparative analysis. Surg Obes Relat Dis 2020; 16: 852-862
  97. Paganelli FL, Luyer M, Hazelbag CM et al. Roux-Y gastric bypass and sleeve gastrectomy directly change gut microbiota composition independent of surgery type. Sci Rep 2019; 9: 10979
  98. Calabrese FM, Disciglio V, Franco I et al. A low glycemic index mediterranean diet combined with aerobic physical activity rearranges the gut microbiota signature in NAFLD patients. Nutrients 2022; 14: 1773
  99. Sharpton SR, Maraj B, Harding-Theobald E et al. Gut microbiome- targeted therapies in nonalcoholic fatty liver disease: a systematic review, meta-analysis, and meta-regression. Am J Clin Nutr 2019; 110: 139-149
  100. Pinheiro TA, Barcala-Jorge AS, Andrade JMO et al. Obesity and malnutrition similarly alter the renin-angiotensin system and inflammation in mice and human adipose. J Nutr Biochem 2017; 48: 74-82
  101. Fu Z, Wang F, Liu X et al. Soluble (pro)renin receptor induces endothelial dysfunction and hypertension in mice with diet-induced obesity via activation of angiotensin II type 1 receptor. Clin Sci (Lond) 2021; 135: 793-810
  102. Faloia E, Gatti C, Camilloni MA et al. Comparison of circulating and local adipose tissue renin-angiotensin system in normotensive and hypertensive obese subjects. J Endocrinol Invest 2002; 25: 309-314
  103. Engeli S, Böhnke J, Gorzelniak K et al. Weight loss and the renin- angiotensin-aldosterone system. Hypertension 2005; 45: 356-362
  104. Park SY, Karki S, Saggese SM et al. Angiotensin II-mediated vasoconstriction of the visceral adipose tissue vasculature is linked to systemic hypertension in obesity. FASEB J 2017; 31: 684.686- 684.686
  105. Oliveras A, Molina L, Goday A et al. Effect of bariatric surgery on cardiac structure and function in obese patients: role of the renin-angiotensin system. J Clin Hypertens (Greenwich) 2021; 23: 181-192
  106. Oliveras A, Galceran I, Goday A et al. Improvement of arterial stiffness one month after bariatric surgery and potential mechanisms. J Clin Med 2021; 10: 691
  107. Yoneda M, Hotta K, Nozaki Y et al. Association between angiotensin II type 1 receptor polymorphisms and the occurrence of nonalcoholic fatty liver disease. Liver Int 2009; 29: 1078-1085
  108. Goh GB, Pagadala MR, Dasarathy J et al. Renin-angiotensin system and fibrosis in non-alcoholic fatty liver disease. Liver Int 2015; 35: 979-985
  109. Sturzeneker MCS, de Noronha L, Olandoski M et al. Ramipril significantly attenuates the development of non-alcoholic steatohepatitis in hyperlipidaemic rabbits. Am J Cardiovasc Dis 2019; 9: 8-17
  110. Hirose A, Ono M, Saibara T et al. Angiotensin II type 1 receptor blocker inhibits fibrosis in rat nonalcoholic steatohepatitis. Hepatology 2007; 45: 1375-1381
  111. Frantz ED, Penna-de-Carvalho A, Batista Tde M et al. Comparative effects of the renin-angiotensin system blockers on nonalcoholic fatty liver disease and insulin resistance in C57BL/6 mice. Metab Syndr Relat Disord 2014; 12: 191-201
  112. Lee KC, Hsieh YC, Yang YY et al. Aliskiren reduces hepatic steatosis and epididymal fat mass and increases skeletal muscle insulin sensitivity in high-fat diet-fed mice. Sci Rep 2016; 6: 18899
  113. Kim KM, Roh JH, Lee S et al. Clinical implications of renin-angiotensin system inhibitors for development and progression of non-alcoholic fatty liver disease. Sci Rep 2021; 11: 2884
  114. Wu Y, Ma KL, Zhang Y et al. Lipid disorder and intrahepatic renin-angiotensin system activation synergistically contribute to non-alcoholic fatty liver disease. Liver In 2016; 36: 1525-1534
  115. Yang M, Ma X, Xuan X et al. Liraglutide attenuates non-alcoholic fatty liver disease in mice by regulating the local renin-angiotensin system. Front Pharmacol 2020; 11: 432
  116. Song LN, Liu JY, Shi TT et al. Angiotensin-(1-7), the product of ACE2 ameliorates NAFLD by acting through its receptor Mas to regulate hepatic mitochondrial function and glycolipid metabolism. FASEB J 2020; 34: 16291-16306
  117. Cao X, Song LN, Zhang YC et al. Angiotensin-converting enzyme 2 inhibits endoplasmic reticulum stress-associated pathway to preserve nonalcoholic fatty liver disease. Diabetes Metab Res Rev 2019; 35: e3123
  118. Cao X, Yang F, Shi T et al. Angiotensin-converting enzyme 2/ angiotensin-(1-7)/Mas axis activates Akt signaling to ameliorate hepatic steatosis. Sci Rep 2016; 6: 21592
  119. Zhang X, Wong GL, Yip TC et al. Angiotensin-converting enzyme inhibitors prevent liver-related events in nonalcoholic fatty liver disease. Hepatology 2021; 76: 469-482
  120. Tai C, Gan T, Zou L et al. Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on cardiovascular events in patients with heart failure: a meta-analysis of randomized controlled trials. BMC Cardiovasc Disord 2017; 17: 257
  121. van Vark LC, Bertrand M, Akkerhuis KM et al. Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of renin-angiotensin-aldosterone system inhibitors involving 158,998 patients. Eur Heart J 2012; 33: 2088-2097
  122. McAlister FA. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are beneficial in normotensive atherosclerotic patients: a collaborative meta-analysis of randomized trials. Eur Heart J 2012; 33: 505-514
  123. Evans M, Carrero JJ, Szummer K et al. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in myocardial infarction patients with renal dysfunction. J Am Coll Cardiol 2016; 67: 1687-1697
  124. Sim HW, Zheng H, Richards AM et al. Beta-blockers and renin- angiotensin system inhibitors in acute myocardial infarction managed with inhospital coronary revascularization. Sci Rep 2020; 10: 15184
  125. Liu T, Wen H, Li H et al. Oleic acid attenuates Ang II (Angiotensin II)-induced cardiac remodeling by inhibiting FGF23 (Fibroblast Growth Factor 23) expression in mice. Hypertension 2020; 75: 680-692
  126. Tian Y, Luo J, Xu Q et al. Macrophage depletion protects against endothelial dysfunction and cardiac remodeling in angiotensin II hypertensive mice. Clin Exp Hypertens 2021; 43: 699-706
  127. Ding J, Tang Q, Luo B et al. Klotho inhibits angiotensin II-induced cardiac hypertrophy, fibrosis, and dysfunction in mice through suppression of transforming growth factor-β1 signaling pathway. Eur J Pharmacol 2019; 859: 172549
  128. Meijles DN, Cull JJ, Markou T et al. Redox regulation of cardiac ASK1 (Apoptosis Signal-Regulating Kinase 1) controls p38-MAPK (Mitogen-Activated Protein Kinase) and orchestrates cardiac remodeling to hypertension. Hypertension 2020; 76: 1208-1218
  129. Leifheit-Nestler M, Kirchhoff F, Nespor J et al. Fibroblast growth factor 23 is induced by an activated renin-angiotensin-aldosterone system in cardiac myocytes and promotes the pro-fibrotic crosstalk between cardiac myocytes and fibroblasts. Nephrol Dial Transplant 2018; 33: 1722-1734
  130. Yang C, Wu X, Shen Y et al. Alamandine attenuates angiotensin II-induced vascular fibrosis via inhibiting p38 MAPK pathway. Eur J Pharmacol 2020; 883: 173384
  131. Kwaifa IK, Bahari H, Yong YK et al. Endothelial dysfunction in obesity-induced inflammation: molecular mechanisms and clinical implications. Biomolecules 2020; 10: 291
  132. Steven S, Dib M, Hausding M et al. CD40L controls obesity-associated vascular inflammation, oxidative stress, and endothelial dysfunction in high fat diet-treated and db/db mice. Cardiovasc Res 2018; 114: 312-323
  133. Muñoz M, López-Oliva ME, Rodríguez C et al. Differential contribution of Nox1, Nox2 and Nox4 to kidney vascular oxidative stress and endothelial dysfunction in obesity. Redox Biol 2020; 28: 101330
  134. Huby AC, Otvos L Jr., Belin de Chantemèle EJ. Leptin induces hypertension and endothelial dysfunction via aldosterone-dependent mechanisms in obese female mice. Hypertension 2016; 67: 1020-1028
  135. Stepp DW, Boesen EI, Sullivan JC et al. Obesity augments vasoconstrictor reactivity to angiotensin II in the renal circulation of the Zucker rat. Am J Physiol Heart Circ Physiol 2007; 293: H2537- H2542
  136. Hartopo AB, Fachiroh J, Puspitawati I et al. Serum endothelin-1 level positively correlates with waist and hip circumferences in stable coronary artery disease patients. Rev Cardiovasc Med 2021; 22: 919-924
  137. Iantorno M, Schinzari F, Mores N et al. Changes in vasodilator reactivity and vasoconstrictor tone in metabolically healthy obesity and the metabolic syndrome. Circulation 2015; 132: A18950- A18950
  138. Jenkins HN, Williams LJ, Dungey A et al. Elevated plasma endothelin-1 is associated with reduced weight loss post vertical sleeve gastrectomy. Surg Obes Relat Dis 2019; 15: 1044-1050
  139. Al-Hamoudi W, Alsadoon A, Hassanian M et al. Endothelial dysfunction in nonalcoholic steatohepatitis with low cardiac disease risk. Sci Rep 2020; 10: 8825
  140. Sapmaz F, Uzman M, Basyigit S et al. Steatosis grade is the most important risk factor for development of endothelial dysfunction in NAFLD. Medicine (Baltimore) 2016; 95: e3280
  141. Theofilis P, Vordoni A, Nakas N et al. Endothelial dysfunction in nonalcoholic fatty liver disease: a systematic review and meta- analysis. Life (Basel) 2022; 12: 718
  142. Lugo-Gavidia LM, Burger D, Matthews VB et al. Role of microparticles in cardiovascular disease: implications for endothelial dysfunction, thrombosis, and inflammation. Hypertension 2021; 77: 1825-1844
  143. Benincasa G, Coscioni E, Napoli C. Cardiovascular risk factors and molecular routes underlying endothelial dysfunction: Novel opportunities for primary prevention. Biochem Pharmacol 2022; 202: 115108
  144. Xu Y, Arora RC, Hiebert BM et al. Non-invasive endothelial function testing and the risk of adverse outcomes: a systematic review and meta-analysis. Eur Heart J Cardiovasc Imaging 2014; 15: 736-746
  145. Ras RT, Streppel MT, Draijer R et al. Flow-mediated dilation and cardiovascular risk prediction: a systematic review with meta- analysis. Int J Cardiol 2013; 168: 344-351
  146. Guo Q, Furuta K, Lucien F et al. Integrin β(1)-enriched extracellular vesicles mediate monocyte adhesion and promote liver inflammation in murine NASH. J Hepatol 2019; 71: 1193-1205
  147. Pasarín M, La Mura V, Gracia-Sancho J et al. Sinusoidal endothelial dysfunction precedes inflammation and fibrosis in a model of NAFLD. PloS One 2012; 7: e32785
  148. Nozaki Y, Fujita K, Wada K et al. Deficiency of eNOS exacerbates early-stage NAFLD pathogenesis by changing the fat distribution. BMC Gastroenterol 2015; 15: 177
  149. Persico M, Masarone M, Damato A et al. "Non alcoholic fatty liver disease and eNOS dysfunction in humans". BMC Gastroenterol 2017; 17: 35
  150. Sheldon RD, Meers GM, Morris EM et al. eNOS deletion impairs mitochondrial quality control and exacerbates Western diet-induced NASH. Am J Physiol Endocrinol Metab 2019; 317: E605-E616
  151. Albadawy R, Agwa SHA, Khairy E et al. Circulatory endothelin 1-regulating RNAs panel: promising biomarkers for non-invasive NAFLD/NASH diagnosis and stratification: clinical and molecular pilot study. Genes (Basel) 2021; 12: 1813
  152. Okamoto T, Koda M, Miyoshi K et al. Antifibrotic effects of ambrisentan, an endothelin-A receptor antagonist, in a non-alcoholic steatohepatitis mouse model. World J Hepatol 2016; 8: 933-941
  153. Simons N, Bijnen M, Wouters KAM et al. The endothelial function biomarker soluble E-selectin is associated with nonalcoholic fatty liver disease. Liver Int 2020; 40: 1079-1088
  154. Laird CT, Hassanein W, O'Neill NA et al. P-and E-selectin receptor antagonism prevents human leukocyte adhesion to activated porcine endothelial monolayers and attenuates porcine endothelial damage. Xenotransplantation 2018; 25: e12381
  155. Bae CR, Zhang H, Kwon YG. The endothelial dysfunction blocker CU06-1004 ameliorates choline-deficient l-amino acid diet-induced non-alcoholic steatohepatitis in mice. PloS One 2020; 15: e0243497
  156. Eslam M, Newsome PN, Sarin SK et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol 2020; 73: 202-209
  157. Eslam M, Sarin SK, Wong VW et al. The Asian pacific association for the study of the liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease. Hepatol Int 2020; 14: 889-919
  158. Moon JH, Kim W, Koo BK et al. Metabolic dysfunction-associated fatty liver disease predicts long-term mortality and cardiovascular disease. Gut Liver 2022; 16: 433
  159. Yoo TK, Lee MY, Kim SH et al. Comparison of cardiovascular mortality between MAFLD and NAFLD: a cohort study. Nutr Metab Cardiovasc Dis 2023; 33: 947-955
  160. Kim H, Lee CJ, Ahn SH et al. MAFLD predicts the risk of cardiovascular disease better than NAFLD in asymptomatic subjects with health check-ups. Digest Dis Sci 2022; 67: 4919-4928
  161. Lee H, Lee YH, Kim SU et al. Metabolic dysfunction-associated fatty liver disease and incident cardiovascular disease risk: a nationwide cohort study. Clin Gastroenterol hHepatol 2021; 19: 2138-2147. e2110
  162. Lin S, Huang J, Wang M et al. Comparison of MAFLD and NAFLD diagnostic criteria in real world. Liver Int 2020; 40: 2082-2089
  163. Carreres L, Jílková ZM, Vial G et al. Modeling diet-induced NAFLD and NASH in rats: a comprehensive review. Biomedicines 2021; 9: 378
  164. Sabir U, Irfan HM , Alamgeer et al. Reduction of hepatic steatosis, oxidative stress, inflammation, ballooning and insulin resistance after therapy with safranal in NAFLD animal model: a new approach. J Inflam Res 2022; 15: 1293-1316
  165. Eng JM, Estall JL. Diet-induced models of non-alcoholic fatty liver disease: food for thought on sugar, fat, and cholesterol. Cells 2021; 10: 1805
  166. Zakaria Z, Othman ZA, Suleiman JB et al. Hepatoprotective effect of bee bread in metabolic dysfunction-associated fatty liver disease (MAFLD) rats: impact on oxidative stress and inflammation. Antioxidants (Basel, Switzerland) 2021; 10: 2031
  167. Cioffi F, Giacco A, Petito G et al. Altered mitochondrial quality control in rats with metabolic dysfunction-associated fatty liver disease (MAFLD) induced by high-fat feeding. Genes (Basel) 2022; 13: 315
  168. Huang Y, Wang C, Wang M et al. Oroxin B improves metabolic- associated fatty liver disease by alleviating gut microbiota dysbiosis in a high-fat diet-induced rat model. Eur J Pharmacol 2023; 951: 175788

Cited by

Sorted by citations

Authors
Li, M., Cui, M., Li, G., Liu, Y., Xu, Y., Eftekhar, S. P., & Ala, M.
Affiliations
  • Shandong University of Traditional Chinese Medicine (CN)
  • Babol University of Medical Sciences (IR)
  • Tehran University of Medical Sciences (IR)
ORCID
Venue
Hormone and Metabolic Research
Publisher
Georg Thieme Verlag KG
Published
2024-03-12
Volume
56
Issue
10
Pages
683-696
ISSN
  • 0018-5043 (ISSN-L)
  • 1439-4286
DOI
10.1055/a-2266-1503
OpenAlex
W4394766859
Cited by
37
References
13
Citations by year
2026: 7 · 2025: 28 · 2024: 2
FWCI
2.43
Type
journal article
Language
en
Open access
Locations
  • Hormone and Metabolic Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
Keywords
obesity, non-alcoholic fatty liver disease, atherosclerotic cardiovascular disease, pathophysiological mechanisms, insulin resistance, dyslipidemia, GLP-1 signaling, inflammation, oxidative stress, mitochondrial dysfunction, gut dysbiosis, renin-angiotensin-aldosterone system, endothelial dysfunction, weight loss, bariatric surgery, semaglutide, tirzepatide, retatrutide, metabolic syndrome
MeSH terms
Animals, Cardiovascular Diseases, Humans, Insulin Resistance, Obesity, Renin-Angiotensin System, Oxidative Stress, Atherosclerosis, Non-alcoholic Fatty Liver Disease

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review