Regulation of Interleukin-4 to Carbohydrates and Lipid Metabolism in Hepatocytes

• Main Authors: Yi-Ren Lai, 賴怡任
• Other Authors: Yih-Hsin Chang
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/00312478919915134464

碩士 === 國立陽明大學 === 醫學生物技術暨檢驗學系 === 103 === Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by abnormal hyperglycemia. Liver is one of the major insulin-targeting organs. During fasting state, liver regulates the release of glucose into circulation and triglyceride breakdown into fatty acid as source of energy. Immune response and inflammation are suggested to play important roles in the development of T2DM. Previous study shows that the proinflammatory cytokine IL-6 and THF-α are association with T2DM, however, the exact diabetic etiology remains unknown. Our previous studies identify the novel role of the immunoregulatory cytokine interleukin-4 (IL-4) in promoting energy catabolism by promoting insulin sensitivity and glucose tolerance, and inhibiting lipid deposits in adipocytes. The aim of this study was to investigate the effects of IL-4 on carbohydrates and lipid metabolism in hepatocytes. Our results showed that IL-4 up-regulated the levels of phosphorylated Akt Ser473 and glycogen synthase kinase-3 α/β Ser21/9, which indicated that IL-4 may promote glycogen synthesis through boosting insulin signaling. Expression of glucose transporter 2 was also elevated by IL-4, suggesting IL-4 promotes glucose uptake in hepatocytes. While IL-4 down-regulated the levels of phosphorylated acetyl-CoA carboxylase 1, it promoted the expression of fatty acid synthase and diglyceride acyltransferase 2, which implies IL-4 modulates de novo lipogenesis. In addition, IL-4 down-regulated the expression levels of fatty acid. On the other hand, IL-4 promoted the expression levels of triglycerides. The above results strongly suggest that IL-4 may promote hepatic energy deposits by potentiating glycogen synthesis and de novo lipogenesis via mediating insulin signal.