Reactive oxygen species‐induced changes in glucose and lipid metabolism contribute to the accumulation of cholesterol in the liver during aging

• Published in: Aging cell Vol. 18; no. 2; pp. e12895 - n/a
• Main Authors: Seo, Eunhui, Kang, Hwansu, Choi, Hojung, Choi, Woohyuk, Jun, Hee‐Sook
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.04.2019; John Wiley and Sons Inc
• Subjects: Aging; Animals; Cholesterol; Cholesterol - metabolism; Chronic diseases; Dextrose; Fatty liver; Free radicals (Chemistry); Gene expression; Glucose; Glucose - metabolism; Glucose transporter; Glycolysis; Hep G2 Cells; Hepatocytes; Hepatocytes - cytology; Hepatocytes - metabolism; Humans; Hydrogen peroxide; Lipid Metabolism; Lipids; Lipids - analysis; Liver; Liver - cytology; Liver - metabolism; Liver diseases; Male; Metabolism; Mice; Mice, Inbred C57BL; Original Paper; Original Papers; Physiological aspects; Reactive oxygen species; Reactive Oxygen Species - analysis; Reactive Oxygen Species - metabolism; RNA; Tumor Cells, Cultured; cholesterol; aging; liver; lipid metabolism; reactive oxygen species
• ISSN: 1474-9718; 1474-9726
• DOI: 10.1111/acel.12895

Aging is a major risk factor for many chronic diseases due to increased vulnerability to external stress and susceptibility to disease. Aging is associated with metabolic liver disease such as nonalcoholic fatty liver. In this study, we investigated changes in lipid metabolism during aging in mice and the mechanisms involved. Lipid accumulation was increased in liver tissues of aged mice, particularly cholesterol. Increased uptake of both cholesterol and glucose was observed in hepatocytes of aged mice as compared with younger mice. The mRNA expression of GLUT2, GK, SREBP2, HMGCR, and HMGCS, genes for cholesterol synthesis, was gradually increased in liver tissues during aging. Reactive oxygen species (ROS) increase with aging and are closely related to various aging‐related diseases. When we treated HepG2 cells and primary hepatocytes with the ROS inducer, H2O2, lipid accumulation increased significantly compared to the case for untreated HepG2 cells. H2O2 treatment significantly increased glucose uptake and acetyl‐CoA production, which results in glycolysis and lipid synthesis. Treatment with H2O2 significantly increased the expression of mRNA for genes related to cholesterol synthesis and uptake. These results suggest that ROS play an important role in altering cholesterol metabolism and consequently contribute to the accumulation of cholesterol in the liver during the aging process.