PMID- 24347527 OWN - NLM STAT- MEDLINE DCOM- 20141028 LR - 20220310 IS - 1539-7262 (Electronic) IS - 0022-2275 (Print) IS - 0022-2275 (Linking) VI - 55 IP - 3 DP - 2014 Mar TI - Interleukin-4 regulates lipid metabolism by inhibiting adipogenesis and promoting lipolysis. PG - 385-97 LID - 10.1194/jlr.M041392 [doi] AB - 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-gamma and CCAAT/enhancer-binding protein-alpha. 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. FAU - Tsao, Chang-Hui AU - Tsao CH AD - Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan. FAU - Shiau, Ming-Yuh AU - Shiau MY FAU - Chuang, Pei-Hua AU - Chuang PH FAU - Chang, Yih-Hsin AU - Chang YH FAU - Hwang, Jaulang AU - Hwang J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131217 PL - United States TA - J Lipid Res JT - Journal of lipid research JID - 0376606 RN - 0 (CCAAT-Enhancer-Binding Protein-alpha) RN - 0 (Carrier Proteins) RN - 0 (PPAR gamma) RN - 0 (Perilipin-1) RN - 0 (Phosphoproteins) RN - 0 (STAT6 Transcription Factor) RN - 0 (Stat6 protein, mouse) RN - 207137-56-2 (Interleukin-4) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) RN - EC 3.1.1.13 (Sterol Esterase) SB - IM MH - 3T3-L1 Cells MH - Adipogenesis/*drug effects/genetics MH - Animals MH - Blotting, Western MH - CCAAT-Enhancer-Binding Protein-alpha/genetics/metabolism MH - Carrier Proteins/metabolism MH - Cyclic AMP-Dependent Protein Kinases/metabolism MH - Gene Expression/drug effects MH - Interleukin-4/*pharmacology MH - Lipid Metabolism/*drug effects/genetics MH - Lipolysis/*drug effects/genetics MH - Mice MH - Microscopy, Confocal MH - PPAR gamma/genetics/metabolism MH - Perilipin-1 MH - Phosphoproteins/metabolism MH - Phosphorylation/drug effects MH - Protein Transport/drug effects MH - RNA Interference MH - Reverse Transcriptase Polymerase Chain Reaction MH - STAT6 Transcription Factor/genetics/metabolism MH - Signal Transduction/drug effects/genetics MH - Sterol Esterase/metabolism PMC - PMC3934724 OTO - NOTNLM OT - CCAAT/enhancer-binding protein-alpha OT - hormone sensitive lipase OT - perilipin OT - peroxisome proliferator-activated receptor-gamma EDAT- 2013/12/19 06:00 MHDA- 2014/10/29 06:00 PMCR- 2014/03/01 CRDT- 2013/12/19 06:00 PHST- 2013/12/19 06:00 [entrez] PHST- 2013/12/19 06:00 [pubmed] PHST- 2014/10/29 06:00 [medline] PHST- 2014/03/01 00:00 [pmc-release] AID - S0022-2275(20)37673-2 [pii] AID - m041392 [pii] AID - 10.1194/jlr.M041392 [doi] PST - ppublish SO - J Lipid Res. 2014 Mar;55(3):385-97. doi: 10.1194/jlr.M041392. Epub 2013 Dec 17.