The Mechanism of Interleukin-6-induced Lipolysis in 3T3-L1 Adipocytes

• Main Authors: Ke-Chun Wu, 吳克俊
• Other Authors: Low-Tone Ho
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/77485619034916894115

碩士 === 國立陽明大學 === 生理學研究所 === 100 === Obesity, characterized by excess fat accumulation, has become a major worldwide health problem. Dysregulation of triglycerides breakdown (i.e., lipolysis) in adipose tissue results in elevated level of circulating free fatty acid and consequently associated with insulin resistance and obesity. Two key lipases naming hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) are responsible for lipolysis. HSL was considered as the rate-limiting enzyme of lipolysis. Phosphorylation of HSL at Ser563, Ser659, Ser660, and Ser600 contributes to lipolytic activation of HSL. ATGL associates with a co-activator protein called comparative gene identification 58 alpha/beta-hydrolase domain containing protein 5 (CGI-58/ABHD-5) to initiate lipolysis. Beyond the classical cAMP/PKA pathway, other signaling are also involved in controlling lipolysis, such as cGMP-dependent and ERK pathway. Interleukin-6 (IL-6) is expressed not only in immune cells but also in adipocytes. In obese patients, the plasma level of IL-6 was elevated. Besides, recent studies have shown that IL-6 could stimulate lipolysis in both human and rodent adipocytes. However, the underlying mechanism of IL-6-induced lipolysis is still unknown. In the current study, well-differentiated 3T3-L1 adipocytes were applied as the cell model. Results showed that treatment of isoproterenol (10 nM) or IL-6 (25, 50, 75, and 100 ng/ml) for 4 hours increased lipolysis in 3T3-L1 adipocytes as measured by glycerol concentration in the medium. Furthermore, IL-6 induced HSL (Ser660) and ERK phosphorylation as examined by Western blotting. Moreover, pretreatment of guanylyl cyclase (GC) inhibitor (LY83583), ERK inhibitor (PD98059) or cGMP-dependent protein kinase (PKG) inhibitor (KT5823) could attenuate IL-6-induced lipolysis. Besides, pretreatment of LY83583 also decreased IL-6-induced HSL (Ser660) or ERK phosphorylation. Meanwhile, treatment of IL-6 (50 ng/ml) increased the interaction between ATGL and ABHD-5 as proven by results of immunoprecipitation. However, IL-6 at 50 ng/ml did not affect the total protein expression of ATGL within 60 minutes based on results of Western blotting. Altogether, IL-6 treatment can induce lipolysis through GC/cGMP pathway and/or partially via ERK. Moreover, HSL and ATGL are both involved in IL-6-induced lipolysis.