Dexmedetomidine attenuates high-fat diet-induced metabolic dysfunction-associated steatotic liver disease in rats by...

Steatosis is the accumulation of neutral lipids in the cytoplasm. Metabolic dysfunction-associated steatotic liver disease (MASLD) is a suitable acronym to define steatosis associated with metabolic dysfunction. Autophagy is a conserved quality-control process in lysosomes that destroys cytoplasmic contents. Lipophagy is the process through which autophagy destroys lipid droplets. This study investigates effects of dexmedetomidine (Dex) on MASLD induced by high-fat diet (HFD) in rats. Sprague Dawley rats were fed 60% HFD for 8 weeks, and Dex (1 mcg/kg/day and 5 mcg/kg/day) was given intraperitoneally. Dex decreased liver integrity markers and improved antioxidant status by decreasing malondialdehyde (MDA). In addition, it decreased serum levels of both total cholesterol and triglycerides. Autophagic markers (Beclin 1, ULK1, AMPK, LC3) were improved by Dex treatment and protein expression of p62 was decreased in a dose-dependent manner. Finally, it decreased apoptosis by decreasing caspsae-3 and increasing Bcl-2. Histopathological examination was used to assess the degree of steatosis. Dex was found to induce autophagy in MASLD in a dose-dependent manner and improve liver function and degree of steatosis. Dex, therefore, may be a potential adjunctive therapeutic option in clinical settings for treating MASLD.