Yang Yongqing, Ju Dapeng, Zhang Mingtao, Yang Gongshe
Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, 22 Xinong Road, Yangling, Shaanxi Province 712100, People's Republic of China.
Endocrine. 2008 Jun;33(3):261-9. doi: 10.1007/s12020-008-9085-7.
Interleukin (IL)-6 stimulates lipolysis in human and rodents adipocytes. However, the mechanism regulating this process is little known. In this study, we demonstrated that IL-6 increased lipolysis in differentiated porcine adipocytes by activation of extracellular signal-related kinase (ERK), which was inhibited by specific ERK inhibitor PD98059. IL-6 treatment did not elevate intracellular cAMP and specific PKA inhibitor H89 did not affect IL-6-induced lipolysis, which suggested that protein kinase A (PKA) pathway was not involved in IL-6-induced lipolysis. Also, the expressions of perilipin A and PPARgamma2 were significantly reduced in response to IL-6 treatment, but the expressions of peroxisome proliferators-activated receptor gamma coactivator-1 alpha (PGC-1alpha), carnitinepalmitoyl-transferase-1 (CPT-1), and uncoupling protein 2 (UCP2) were significantly elevated. In conclusion, these results suggested that chronic high dose of IL-6 directly stimulated lipolysis in porcine adipocytes through activation of ERK, subsequently repressing perilipin A and promoting PGC-1alpha expression.
白细胞介素(IL)-6可刺激人和啮齿动物脂肪细胞的脂肪分解。然而,调节这一过程的机制却鲜为人知。在本研究中,我们证明IL-6通过激活细胞外信号相关激酶(ERK)增加了分化猪脂肪细胞的脂肪分解,而ERK特异性抑制剂PD98059可抑制这一过程。IL-6处理并未提高细胞内cAMP水平,特异性蛋白激酶A(PKA)抑制剂H89也不影响IL-6诱导的脂肪分解,这表明PKA途径不参与IL-6诱导的脂肪分解。此外,响应IL-6处理,围脂滴蛋白A和PPARγ2的表达显著降低,但过氧化物酶体增殖物激活受体γ辅激活因子-1α(PGC-1α)、肉碱棕榈酰转移酶-1(CPT-1)和解偶联蛋白2(UCP2)的表达显著升高。总之,这些结果表明,慢性高剂量IL-6通过激活ERK直接刺激猪脂肪细胞的脂肪分解,随后抑制围脂滴蛋白A并促进PGC-1α表达。