Metabolic-Dysfunction-Associated Steatotic Liver Disease—Its Pathophysiology, Association with Atherosclerosis and Cardiovascular Disease, and Treatments

• Published in: International journal of molecular sciences Vol. 24; no. 20; p. 15473
• Main Authors: Yanai, Hidekatsu, Adachi, Hiroki, Hakoshima, Mariko, Iida, Sakura, Katsuyama, Hisayuki
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.10.2023; MDPI
• Subjects: Adipose tissues; Atherosclerosis; Blood pressure; Body fat; Body mass index; Body weight; Cardiac patients; Cardiovascular disease; Development and progression; Diabetes; Drug therapy; Enzymes; Fatty acids; Fenofibrate; Glucose; Glucose metabolism; Health aspects; High density lipoprotein; Homeopathy; Hypertension; Insulin; Insulin resistance; Lipids; Lipoproteins; Liver diseases; Materia medica and therapeutics; Meta-analysis; Metabolic disorders; Metabolic syndrome; metabolic-dysfunction-associated steatotic liver disease; Musculoskeletal system; Obesity; Oxidation; Pathogenesis; pemafibrate; Physiological aspects; Proteins; Review; Risk factors; Surgery; Synthesis; Therapeutics; triglyceride; Tumor necrosis factor-TNF; Type 2 diabetes
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms242015473

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease that affects more than a quarter of the global population and whose prevalence is increasing worldwide due to the pandemic of obesity. Obesity, impaired glucose metabolism, high blood pressure and atherogenic dyslipidemia are risk factors for MASLD. Therefore, insulin resistance may be closely associated with the development and progression of MASLD. Hepatic entry of increased fatty acids released from adipose tissue, increase in fatty acid synthesis and reduced fatty acid oxidation in the liver and hepatic overproduction of triglyceride-rich lipoproteins may induce the development of MASLD. Since insulin resistance also induces atherosclerosis, the leading cause for death in MASLD patients is cardiovascular disease. Considering that the development of cardiovascular diseases determines the prognosis of MASLD patients, the therapeutic interventions for MASLD should reduce body weight and improve coronary risk factors, in addition to an improving in liver function. Lifestyle modifications, such as improved diet and increased exercise, and surgical interventions, such as bariatric surgery and intragastric balloons, have shown to improve MASLD by reducing body weight. Sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to improve coronary risk factors and to suppress the occurrence of cardiovascular diseases. Both SGLT2i and GLP-1 have been reported to improve liver enzymes, hepatic steatosis and fibrosis. We recently reported that the selective peroxisome proliferator-activated receptor-alpha (PPARα) modulator pemafibrate improved liver function. PPARα agonists have multiple anti-atherogenic properties. Here, we consider the pathophysiology of MASLD and the mechanisms of action of such drugs and whether such drugs and the combination therapy of such drugs could be the treatments for MASLD.