Mechanism of Interleukin-4 Reducing Lipid Deposit by Regulating Hormone-Sensitive Lipase

被引:37
作者
Shiau, Ming-Yuh [1 ]
Chuang, Pei-Hua [2 ]
Yang, Ching-Ping [2 ]
Hsiao, Chiao-Wan [2 ,3 ,4 ]
Chang, Shu-Wen [2 ]
Chang, Kai-Yun [2 ]
Liu, Tsung-Ming [2 ]
Chen, Huan-Wen [2 ]
Chuang, Cheng-Chieh [2 ]
Yuan, Sheau-Yun [1 ,5 ]
Chang, Yih-Hsin [2 ]
机构
[1] Hungkuang Univ, Dept Nursing, Coll Nursing, Taichung, Taiwan
[2] Natl Yang Ming Univ, Dept Biotechnol & Lab Sci Med, Taipei, Taiwan
[3] Natl Yang Ming Univ, Program Mol Med, Taipei, Taiwan
[4] Acad Sinica, Taipei, Taiwan
[5] Taichung Vet Gen Hosp, Div Urol, Dept Surg, Taichung, Taiwan
关键词
INFLAMED ADIPOSE-TISSUE; INSULIN SENSITIVITY; IL-4; OBESITY; METABOLISM; PATHOGENESIS; ASSOCIATION; EXPRESSION; RESISTANCE;
D O I
10.1038/s41598-019-47908-9
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Accumulating evidence indicates that inflammation participates in the pathophysiological progress from insulin resistance, obesity, metabolic abnormalities, and type 2 diabetes mellitus. Our previous study reveals that interleukin-4 (IL-4) inhibits adipogenesis and promotes lipolysis to decrease lipid deposits by enhancing the activity of hormone sensitive lipase (HSL). The present study further dissects and characterizes the molecular mechanism of IL-4 in regulating HSL expression and lipolytic activity in the terminal differentiated 3T3-L1 mature adipocytes. Our results showed that IL-4 increased cAMP which then enhanced PKA activity and subsequent phosphorylation of HSL and perilipin. The phosphorylated HSL (p-HSL) translocated from cytoplasm to the surface of lipid droplets and exhibited lipolytic function. After being phosphorylated, p-perilipin also facilitated lipolysis through interacting with p-HSL. The in vitro findings were further verified by in vivo study in which IL-4 exhibited prolipolytic activity and enhanced HSL activity. In summary, the net outcome of IL-4 treatment is to reduce lipid storage by promoting lipolysis through enhancing HSL activity via cAMP/PKA pathway, the major route leading to lipolysis.
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页数:11
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