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Tsao, CH, Shiau, MY, Chuang, PH, Chang, YH and Hwang, J (2014) Interleukin-4 regulates lipid metabolism by inhibiting adipogenesis and promoting lipolysis. J. Lipid Res. 55:385-97


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.


PubMed PMC3934724 Online version:10.1194/jlr.M041392


3T3-L1 Cells; Adipogenesis/drug effects; Adipogenesis/genetics; Animals; Blotting, Western; CCAAT-Enhancer-Binding Protein-alpha/genetics; CCAAT-Enhancer-Binding Protein-alpha/metabolism; Carrier Proteins/metabolism; Cyclic AMP-Dependent Protein Kinases/metabolism; Gene Expression/drug effects; Interleukin-4/pharmacology; Lipid Metabolism/drug effects; Lipid Metabolism/genetics; Lipolysis/drug effects; Lipolysis/genetics; Mice; Microscopy, Confocal; PPAR gamma/genetics; PPAR gamma/metabolism; Phosphoproteins/metabolism; Phosphorylation/drug effects; Protein Transport/drug effects; RNA Interference; Reverse Transcriptase Polymerase Chain Reaction; STAT6 Transcription Factor/genetics; STAT6 Transcription Factor/metabolism; Signal Transduction/drug effects; Signal Transduction/genetics; Sterol Esterase/metabolism



Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status


GO:0070351: negative regulation of fat cell differentiation



Figure 2, panels C and D show that treatment with IL-4 in the stage of fat cell development where replication occurs is sufficient to inhibit adipogenesis.

CACAO 10416



GO:0070351: negative regulation of white fat cell proliferation

ECO:0000314: direct assay evidence used in manual assertion


Seeded From UniProt



See also


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