Relative Quantitative Comparison between Lipotoxicity and Glucotoxicity Affecting the PARP-NAD-SIRT1 Pathway in Hepatocytes

Cellular Physiology and Biochemistry

关键词: Cytotoxicity;    Free fatty acids;    Hyperglycemia;    Hepatocytes;    Poly (ADP)-ribose polymerase;   

DOI  :  10.1159/000354474

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims Insulin resistance in type 2 diabetes results from a combination of hyperglycemia and elevated free fatty acid (FFA) concentrations. However, the individual effects of glucotoxicity and lipotoxicity on cell function have not been determined. Methods To compare the effects of increased FFAs and glucose levels on the PARP-NAD-SIRT1 pathway, which modulates insulin sensitivity, we cultured HepG2 hepatocytes with 300 or 500 µM oleic acid (OA) or 30 mM glucose for 1-4 days. PARP activity, NAD level, SIRT1 expression and insulin receptor phosphorylation were determined. Results PARP activity was higher while NAD level and SIRT1 expression were lower in OA-treated cells than in control cells. Insulin receptor phosphorylation in response to insulin stimulation was attenuated under OA stimulation. Compared to glucose, OA produced a more rapid effect on the PARP-NAD-SIRT1 pathway in HepG2 cells. The reduction in SIRT1 expression and insulin receptor phosphorylation was similar in cells treated with 500 μM OA for 1 day and those treated with 30 mM glucose for 4 days. In addition to PARP activation, the LXRα activator T0901317 also affected SIRT1 expression. Conclusion FFAs modulated cellular function through multiple ways, and induced more rapid and more potent cytotoxicity than glucose.

【 授权许可】

CC BY-NC-ND