Function And Post-translational Regulation Of Fsp27 In Lipid Metabolism

Metabolic syndromes, particularly obesity, have become major health problems in modern society, which spread from developed to developing countries. Adipose tissue has pivotal role in energy homeostasis and obesity onset and development. Fsp27, a member of CIDE family proteins is crucial in energy metabolism. Fsp27 localizes to lipid droplet surface where it promote neutral lipid storage. Genetic ablation of Fsp27 in mice result in reduced adiposity, mitochondrial proliferation, enhanced basal lipolysis and reduced lipid droplet size. In current research, we define the lipid droplet targeting signal, minimal functional domain and residues critical for lipid droplet size control in Fsp27. Meanwhile, we identify Fsp27 as a crucial regulator of neutral lipid/phospholipid metabolic balance through lipidomics. We further analyze the post-translational regulation of Fsp27 under different physiological conditions. Our data indicate that Fsp27 is rapidly degraded through ubiquitin-proteasome pathway in adipocytes. Interestingly, ubiquitination of Fsp27 is reduced during isoproterenol induced lipolysis in adipocytes. Accordingly, Fsp27 is stabilized. However, the stabilization does not depend upon continuous activation of PKA and is enhanced by exogenous oleic acid, indicating it is a post-lipolytic effect. Meanwhile, stabilized Fsp27 specifically accumulates on dispersed small lipid droplets produced by stimulated lipolysis. Further, the stabilization of Fsp27 relies upon TAG synthesis and nascent lipid droplet packaging on ER. Our data uncover that adipocytes stabilize Fsp27 during stimulated lipolysis which could further restore normal neutral lipid storage.