miR-871-5p/PGC1α Regulates Aging-Induced Lipid Deposition in Hepatocytes Through Fatty AcID-β-Oxidation

作者：Zheng, Ying; Chen, Xiaoling; Lu, Ting; Lin, Zhiyong; Liu, Chaoqi; Yuan, Ding^*; Yuan, Chengfu^*

来源：Journals of Gerontology - Series A Biological Sciences and Medical Sciences, 2023, 78(11): 2007-2015.

DOI：10.1093/gerona/glad185

• Aging
• Fatty acid beta oxidation
• miR-871-5p
• Nonalcoholic fatty liver disease
• Proliferator-activated receptor alpha

This study investigated the role of the miR-871-5p/proliferator-activated receptor alpha (PGC1 alpha) pathway in ameliorating hepatic steatosis. We examined miR-871-5p expression in liver tissues of aging 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 PGC1 alpha 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 aging. 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 PGC1 alpha expression and cause lipid deposition in the liver due to aging. miR-871-5p controls this process by regulating PGC1 alpha/fatty acid beta-oxidation. H&E staining displayed the appearance of fat vacuoles in the livers of aging mice, and fatty acid beta-oxidation-related genes (acyl-coenzyme A oxidase 1 carnitine palmitoyl transferase 1 alpha and peroxisome proliferator-activated receptor alpha) expression was significantly reduced. Lipogenic genes (sterol regulatory element binding protein 1C and fatty acid synthase) expression level was increased in the livers of aging mice. In AML12 cells co-induced by low serum and PA, miR-871-5p mimics decreased PGC1 alpha expression and increased lipid droplet accumulation in senescent hepatocytes. Conversely, miR-871-5p inhibitor promoted PGC1 alpha 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 aging.

• 单位
  中国医科大学