Acetylation of Cavin-1 Promotes Lipolysis in White Adipose Tissue

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.