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

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Abstract
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.
Funding Information
  • Ministry of Education (106AC-P686)
  • University System of Taiwan (VGHUST105-G7-8-1, VGHUST104-G7-8-1)
  • Ministry of Science and Technology, Taiwan (106-2314-B-010-032, 105-2320-B-241-005)

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