Fat-Specific Protein 27 Alpha Inhibits Autophagy-Dependent Lipid Droplet Breakdown In White Adipocytes

Aims/Introduction Fat-specific protein 27 (FSP27) alpha is the major isoform of FSP27 in white adipose tissue (WAT), and is essential for large unilocular lipid droplet (LD) formation in white adipocytes. In contrast, FSP27 beta is abundantly expressed in brown adipose tissue (BAT), and plays an important role in small multilocular LD formation. In FSP27 KO mice in which FSP27 alpha and beta are both depleted, WAT is characterized by multilocular LD formation, and by increased mitochondrial abundance and energy expenditure, whereas BAT conversely manifests large oligolocular LDs and reduced energy expenditure. Materials and Methods We investigated the effects of autophagy in WAT and BAT of wild type (WT) and FSP27 knockout (KO) mice. In addition, we examined the effects of FSP27 alpha and FSP27 beta to the induction of autophagy in COS cells. Results Food deprivation induced autophagy in BAT of WT mice, as well as in WAT of FSP27 KO mice, suggesting that enhanced autophagy is characteristic of adipocytes with small multilocular LDs. Pharmacological inhibition of autophagy attenuated the fasting-induced loss of LD area in adipocytes with small multilocular LDs (BAT of WT mice and WAT of FSP27 KO mice), without affecting that in adipocytes with large unilocular or oligolocular LDs (WAT of WT mice or in BAT of FSP27 KO mice). Overexpression of FSP27 alpha inhibited autophagy induction by serum deprivation in COS cells, whereas that of FSP27 beta had no such effect. Conclusions The present results thus showed that FSP27 alpha inhibits autophagy and might thereby contribute to the energy-storage function of WAT.