Interleukin-4 Boosts Insulin-Induced Energy Deposits by Enhancing Glucose Uptake and Lipogenesis in Hepatocytes

• Published in: Oxidative medicine and cellular longevity Vol. 2018; no. 2018; pp. 1 - 15
• Main Authors: Chang, Yih-Hsin, Chen, Chun-Jung, Hsiao, Chiao-Wan, Ho, Kuo-Ting, Lai, Yi-Ren, Shiau, Ming-Yuh, Yang, Ching-Ping, Lo, Yu-Li
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2018; Hindawi; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Animals; Blotting, Western; Dextrose; Diabetes Mellitus, Type 2 - metabolism; Enzymes; Fatty acids; Glucose; Glucose - metabolism; Glycogen; Hep G2 Cells; Hepatocytes - drug effects; Hepatocytes - metabolism; Humans; Inflammation; Insulin; Insulin - pharmacology; Insulin resistance; Interleukin-4 - pharmacology; Interleukins; Kinases; Lipid Metabolism - drug effects; Male; Mice, Inbred C57BL; Rodents; Signal Transduction - drug effects; Synthesis; Triglycerides; Triglycerides - metabolism; Type 2 diabetes; Taiwan; United States > US
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2018/6923187

Type 2 diabetes mellitus (T2DM), with dysregulated hepatic gluconeogenesis as the major cause of fasting hyperglycemia, is closely associated with chronic inflammation. We previously demonstrated interleukin-4 (IL-4) improves insulin sensitivity and glucose tolerance while reducing lipid deposits. The present study examined the in vitro effects of IL-4 on insulin signaling molecules, glucose uptake, and lipid metabolism in hepatocytes, as well as in vivo effects on hepatic adiposity, for elucidating the roles of IL-4 in hepatic energy metabolism. Potential interaction between IL-4 and insulin in regulating hepatic metabolism was also investigated. Our results showed that IL-4 enhanced Akt and GSK-3α/β phosphorylations, which in turn promoted glycogen synthesis. IL-4 not only potentiated basal glucose uptake by upregulating glucose transporter 2 expression but also promoted insulin-induced glucose uptake. Additionally, IL-4 increased triglyceride contents through facilitating free fatty acid uptake and expression/activity of lipogenic enzymes. The major effects of IL-4 on the liver were to promote energy storage by boosting insulin-stimulated glucose uptake and lipid synthesis. This study provides evidence to implicate the novel roles of IL-4 in mediating hepatic glucose and lipid metabolism, interactions between immune responses and metabolic homeostasis, and the involvement of IL-4 in metabolic abnormalities.