MiR-871-5p / PGC1α regulates aging-induced lipid deposition in hepatocytes through fatty acid β-oxidation.

Abstract

This study investigated the role of the miR-871-5p/proliferator-activated receptor α (PGC1α) pathway in ameliorating hepatic steatosis. We examined miR-871-5p expression in liver tissues of ageing mice and AML12 senescent cells co-induced by low serum and palmitic acid (PA). Bioinformatics and multiple experiments were employed to validate the expression level of the target gene PGC1α for miR-871-5p. In this study, we aimed to investigate the potential role of miR-871-5p in regulating hepatic lipid deposition associated with ageing. To do so, we performed in vitro transfection of both miR-871-5p mimic and inhibitor into senescent hepatocytes. Our results showed that miR-871-5p could inhibit PGC1α expression and cause lipid deposition in the liver due to ageing. MiR-871-5p controls this process by regulating PGC1α / fatty acid β oxidation. H&E staining displayed the appearance of fat vacuoles in the livers of ageing mice, and fatty acid β oxidation-related genes (acyl-coenzyme A oxidase 1 carnitine palmitoyl transferase 1α (ACOX1), and peroxisome proliferator-activated receptor α (PPARα)) expression was significantly reduced. Lipogenic genes (sterol regulatory element binding protein 1C (SREBP-1C), fatty acid synthase (FASN)) expression level was increased in the livers of ageing mice. In AML12 cells co-induced by low serum and PA, miR-871-5p mimics decreased PGC1α expression and increased lipid droplet accumulation in senescent hepatocytes. Conversely, miR-871-5p inhibitor promoted PGC1α expression and reduced lipid deposition in senescent hepatocytes. Our findings suggest that inhibiting miR-871-5p could be crucial in ameliorating aging-associated hepatic steatosis. These findings offer valuable insights into the molecular mechanisms driving hepatic steatosis in ageing.