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Horm Metab Res 2024; 56(10): 683-696
DOI: 10.1055/a-2266-1503
Review

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

Meng Li
1   Department of Endocrinology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
,
Man Cui
1   Department of Endocrinology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
,
Guoxia Li
1   Department of Endocrinology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
,
Yueqiu Liu
2   Clinical Specialty of Integrated Chinese and Western Medicine, The First Clinical School of Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
,
Yunsheng Xu 
1   Department of Endocrinology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
,
Seyed Parsa Eftekhar
3   Department of Pharmacology, Babol University of Medical Science, Babol, Iran
,
Moein Ala
4   Department of Pharmacology, Tehran University of Medical Sciences, Tehran, Iran
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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.

Keywords

obesity  - cardiovascular diseases - insulin resistance - endothelial dysfunction - GLP1 signaling


Publication History

Received: 15 January 2024

Accepted: 02 February 2024

Article published online:
12 March 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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