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

Abstract EN

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.