雌激素受体关联受体α 调节脂肪细胞甘油三酯分解

Role of estrogen-related receptor α in adipocyes lipolysis

摘要:

雌激素受体关联受体α (Estrogen-related receptor α，ERRα) 是调控机体能量代谢的关键转录调控因子，也是脂肪生成的关键调控者。为研究ERRα 对脂肪细胞甘油三酯分解的影响及其分子机制，分化的猪脂肪细胞在PKA (Proteinkinase A) 或/和ERK (Extracellular signal-related kinase) 抑制剂预处理和不处理的情况下，再用Ad-ERRα 侵染或XCT790处理48 h。通过测定脂肪细胞中甘油三酯浓度和培养液中的甘油释放量分析脂肪细胞的脂解变化；Western blotting 方法检测PPARγ (Peroxisome proliferator-activated receptor γ，PPARγ)、perilipin A、p-perilipin A、HSL (Hormone sensitivelipase，HSL) 和ATGL (Adipose triglyceride lipase，ATGL) 蛋白表达。结果显示，ERRα 显著促进猪脂肪细胞分化及甘油三酯积累，同时促进了甘油三酯水解；分别及同时阻断PKA 和ERK 通路并不影响ERRα 对脂肪细胞甘油释放的促进作用；ERRα 显著上调HSL、ATGL、PPARγ 及perilipin A 蛋白表达，但p-perilipin A 水平并未发生变化。推测过量表达ERRα 可能导致HSL 和ATGL 蛋白表达上调并促进甘油三酯水解，从而为脂肪细胞分化提供更多的游离脂肪酸(Free fat acid，FFA) 作为甘油三酯合成周转的底物。

Abstract:

Estrogen-related receptor α (ERRα) is a key regulator for energy metabolism and adipogenesis. However, its role in lipolysis is unknown. To study the function of ERRα in lipolysis, primary cultured differentiated porcine adipocytes were treated by a specific inverse agonist XCT790 or infected with adenoviral vector expressed ERRα for 48 h, in the absence and/or presence of specific protein kinase A (PKA) inhibitor or extracellular signal-related kinase (ERK) inhibitor. Then, we measured the triglyceride (TG) content and the glycerol release into the culture media to analysis the effect of ERRα on lipolysis; Further, we analyzed the expression of PPARγ, perilipin A, p-perilipin A, HSL and ATGL with Western blotting. Here, we found that ERRα significantly increased adipocytes differentiation, TG accumulation and glycerol release. Separately or simultaneously block the PKA and ERK pathway do not significantly altered the effect of ERRα on glycerol release. ERRα significantly up-regulated the proteins expression of PPARγ, perilipin A, HSL and ATGL, while the p-perilipin A protein level was not significantly changed. These findings imply that ERRα could increase lipolysis via up-regulating HSL and ATGL, thereby to supply more FFA as substrate for a larger turnover of cellular triglyceride pool during adipocytes differentiation.