Caveolin-1 and cavins proteins form membrane caveolae, invaginations of the plasma membrane that are particularly abundant adipocytes and endothelial cells within adipose tissue. Caveolin-1 deficiency leads to lipoatrophy in transgenic mice models suggesting a critical role in the control of lipid storage. Studies on Cav-1 deficient mice model (Cav1 (-/-) mice) also revealed important defects in the cardiovascular function, that are rescued by specific reexpression of Cav1 in endothelium (Cav1 RC mice).To address the contribution of endothelial caveolin-1 expression to the lipoatrophic phenotype, we compared metabolic phenotypes observed in Cav1 deficient with those of Cav1 RC and control mice and found a persistent lipoatrophic phenotype in Cav1 (-/-) mice. Considering the key role of caveolin-1 in the control of adipose tissue lipid storage capacity, we chose an overexpression approach of caveolin-1 and cavins 3T3-L1 adipocytes to investigate the underlying molecular mechanisms. All three cell lines contained a higher number of caveolae whereas only caveolin-1 overexpression led to lipid droplet expansion both in vitro and in vivo, suggesting that caveolin-1 control on lipid storage occurs outside of caveolae. In agreement, larger lipid droplets were found in cells expressing a caveolin-1-perilipin-GFP fusion construct, in which exogenous caveolin-1 strictly localized onto lipid droplets. Together our data demonstrate a specific role of lipid droplet caveolin-1 pool, independent of caveolae to modulate lipid droplet expansibility
