Affiliation:
1. Department of Endocrinology, The Second Affiliated Hospital of Shandong
University of Traditional Chinese Medicine, Jinan, China
2. Clinical Specialty of Integrated Chinese and Western Medicine, The
First Clinical School of Medicine, Shandong University of Traditional Chinese
Medicine, Jinan, China
3. Department of Pharmacology, Babol University of Medical Science, Babol,
Iran
4. Department of Pharmacology, Tehran University of Medical Sciences,
Tehran, Iran
Abstract
AbstractObesity, 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.