Interleukin-4 regulates lipid metabolism by inhibiting adipogenesis and promoting lipolysis

Chang Hui Tsao, Ming Yuh Shiau, Pei Hua Chuang, Yih Hsin Chang, Jaulang Hwang

Research output: Contribution to journalArticlepeer-review

99 Citations (Scopus)


Long-term cytokine-mediated inflammation is a risk factor for obesity and type 2 diabetes mellitus (T2DM). Our previous studies reveal significant associations between promoter single nucleotide polymorphisms (SNPs) of interleukin (IL)-4 and T2DM, as well as between SNPs in genes encoding IL-4/IL-4 receptor and high density lipoproteins. Our animal study reveals that IL-4 regulates glucose/lipid metabolism by promoting glucose tolerance and inhibiting lipid deposits. The above results strongly suggest the involvement of IL-4 in energy homeostasis. In the present study, we focus on examining the regulatory mechanism of IL-4 to lipid metabolism. Our results show that IL-4 inhibits adipogenesis by downregulating the expression of peroxisome proliferator- activated receptor-γ and CCAAT/enhancer-binding protein-α. Additionally, IL-4 promotes lipolysis by enhancing the activity and translocation of hormone sensitive lipase (HSL) in mature adipocytes, which suggests that IL-4 plays a pro-lipolytic role in lipid metabolism by boosting HSL activity. Our results demonstrate that IL-4 harbors pro-lipolysis capacity by inhibiting adipocyte differentiation and lipid accumulation as well as by promoting lipolysis in mature adipocytes to decrease lipid deposits. The above findings uncover the novel roles of IL-4 in lipid metabolism and provide new insights into the interactions among cytokine/immune responses, insulin sensitivity, and metabolism.

Original languageEnglish
Pages (from-to)385-397
Number of pages13
JournalJournal of Lipid Research
Issue number3
Publication statusPublished - Mar 2014


  • CCAAT/enhancer-binding protein-α
  • Hormone sensitive lipase
  • Perilipin
  • Peroxisome proliferator-activated receptor-γ

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology


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