激活TRPV1调控SIRT1/ RIP140抑制棕色脂肪白色化预防肥胖的机制

棕色脂肪白色化与肥胖密切相关，阐明其机制对肥胖防治有重要意义。研究表明SIRT1去乙酰化激活PGC-1α抑制白色脂肪生成，RIP140抑制PGC-1α/UCP-1，减少线粒体生成。我们发现肥胖时棕色脂肪白色化与PGC-1α/UCP-1调控线粒体功能有关，激活TRPV1上调棕色脂肪UCP-1/下调RIP140, 但其是否参与PGC-1α调控棕色脂肪白色化尚并不清楚。为此我们假设：肥胖时SIRT1/RIP140轴调节PGC-1α致线粒体功能障碍及能量代谢失衡，促进棕色脂肪白色化；激活TRPV1上调SIRT1/PGC-1α增加棕色脂肪功能，抑制RIP140/PGC-1α阻止棕色脂肪白色化，预防肥胖。 拟从整体和细胞水平阐明SIRT1/ RIP140轴调控PGC-1α抑制棕色脂肪白色化，揭示TRPV1影响SIRT1/RIP140/PGC-1α轴维持棕色脂肪结构与功能正常的机制，为肥胖防治提供新措施

Brown-to-white adipose tissue plays an important role in the genesis of obesity. the mechanism of which was of great significance for the prevention of obesity. It was reported SIRT1 deacetylation suppressed the production of white adipose through activating PGC-1α, While RIP140 was a negative regulator of PGC-1α/ UCP-1 and reduce mitochondria biogenesis. Our research found the brown-to-white adipose tissue existed in obese mice by down-regulation of PGC-1α/ UCP-1 in adipose, activation of TRPV1 channel up-regulated the expression of UCP-1 and down-regulated RIP140 in brown adipose, Activation of TRPV1 up-regulated the expression of UCP-1 and down-regulated RIP140,but whether Sirt1/RIP140 participated in the brown-to-white adipose tissue was unclear. Therefore, we hypothesized SIRT1/RIP140 regulating PGC-1α, which induced the dysfunction of mitochondria and energy metabolism, and then enhanced brown-to-white adipose tissue. Activation of TRPV1 channel by dietary capsaicin could prevent obesity by up-regulating the positive effects of SIRT1/PGC-1α and inhibiting brown-to-white adipose tissue. For testing the hypothesize, we will explore the mechanism of SIRT1/ RIP140 on brown-to-white adipose tissue by mitochondria and uncover the mechanism of TRPV1 maintains the structure and function of brown adipose by SIRT1/ RIP140/PGC-1α. Our study will shed light on new approaches for prevention of obesity.