Acetylation of Cavin-1 Promotes Lipolysis in White Adipose Tissue
Acetylation of Cavin-1 Promotes Lipolysis in White Adipose Tissue
复制标题
Cavin-1 的乙酰化促进白色脂肪组织中的脂肪分解
DOI：
10.1128/mcb.00058-17
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发表时间：
2017
影响因子：
5.3
通讯作者：
Tang Qi Qun
中科院分区：
文献类型：
--
作者：
Zhou Shui Rong;Guo Liang;Wang Xu;Liu Yang;Peng Wan Qiu;Liu Yuan;Wei Xiang Bo;Dou Xin;Ding Meng;Lei Qun Ying;Qian Shu Wen;Li Xi;Tang Qi Qun
摘要白色脂肪组织（WAT）作为一个可逆的能量储存库，以脂质的形式响应营养状况。Cavin-1是小窝生物发生中的重要组分，是脂肪细胞中脂解的正调节剂。然而，cavin-1在脂解调节中的分子机制仍然知之甚少。在这里，我们发现cavin-1在赖氨酸291，293和298（3 K）处被乙酰化，这些赖氨酸在WAT中受到营养调节。我们进一步确定GCN 5为乙酰转移酶，Sirt 1为cavin-1的脱乙酰酶。cavin-1的乙酰化模拟3Q突变体增强了3 T3-L1脂肪细胞和斑马鱼中的脂肪动员。从机制上讲，乙酰化的cavin-1优先与脂肪酶敏感的脂肪酶相互作用，并将其招募到小窝，从而促进脂解。我们的研究结果揭示了cavin-1在WAT中以乙酰化依赖性方式调节脂解中的重要作用。
ABSTRACT White adipose tissue (WAT) serves as a reversible energy storage depot in the form of lipids in response to nutritional status. Cavin-1, an essential component in the biogenesis of caveolae, is a positive regulator of lipolysis in adipocytes. However, molecular mechanisms of cavin-1 in the modulation of lipolysis remain poorly understood. Here, we showed that cavin-1 was acetylated at lysines 291, 293, and 298 (3K), which were under nutritional regulation in WAT. We further identified GCN5 as the acetyltransferase and Sirt1 as the deacetylase of cavin-1. Acetylation-mimetic 3Q mutants of cavin-1 augmented fat mobilization in 3T3-L1 adipocytes and zebrafish. Mechanistically, acetylated cavin-1 preferentially interacted with hormone-sensitive lipase and recruited it to the caveolae, thereby promoting lipolysis. Our findings shed light on the essential role of cavin-1 in regulating lipolysis in an acetylation-dependent manner in WAT.