FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets
Naonobu Nishino, … , Tohru Fushiki, Masato Kasuga
Naonobu Nishino, … , Tohru Fushiki, Masato Kasuga
Published July 24, 2008
Citation Information: J Clin Invest. 2008;118(8):2808-2821. https://doi.org/10.1172/JCI34090.
View: Text | PDF
Research Article

FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets

Abstract

White adipocytes are unique in that they contain large unilocular lipid droplets that occupy most of the cytoplasm. To identify genes involved in the maintenance of mature adipocytes, we expressed dominant-negative PPARγ in 3T3-L1 cells and performed a microarray screen. The fat-specific protein of 27 kDa (FSP27) was strongly downregulated in this context. FSP27 expression correlated with induction of differentiation in cultured preadipocytes, and the protein localized to lipid droplets in murine white adipocytes in vivo. Ablation of FSP27 in mice resulted in the formation of multilocular lipid droplets in these cells. Furthermore, FSP27-deficient mice were protected from diet-induced obesity and insulin resistance and displayed an increased metabolic rate due to increased mitochondrial biogenesis in white adipose tissue (WAT). Depletion of FSP27 by siRNA in murine cultured white adipocytes resulted in the formation of numerous small lipid droplets, increased lipolysis, and decreased triacylglycerol storage, while expression of FSP27 in COS cells promoted the formation of large lipid droplets. Our results suggest that FSP27 contributes to efficient energy storage in WAT by promoting the formation of unilocular lipid droplets, thereby restricting lipolysis. In addition, we found that the nature of lipid accumulation in WAT appears to be associated with maintenance of energy balance and insulin sensitivity.

Authors

Naonobu Nishino, Yoshikazu Tamori, Sanshiro Tateya, Takayuki Kawaguchi, Tetsuro Shibakusa, Wataru Mizunoya, Kazuo Inoue, Riko Kitazawa, Sohei Kitazawa, Yasushi Matsuki, Ryuji Hiramatsu, Satoru Masubuchi, Asako Omachi, Kazuhiro Kimura, Masayuki Saito, Taku Amo, Shigeo Ohta, Tomohiro Yamaguchi, Takashi Osumi, Jinglei Cheng, Toyoshi Fujimoto, Harumi Nakao, Kazuki Nakao, Atsu Aiba, Hitoshi Okamura, Tohru Fushiki, Masato Kasuga

×

Figure 7

Formation of large lipid droplets induced by forced expression of FSP27 in COS cells.

Options: View larger image (or click on image) Download as PowerPoint
Formation of large lipid droplets induced by forced expression of FSP27 ...
(A) Immunoblot analysis of FSP27 and β-actin (loading control) in COS cells 2 days after transfection with an expression plasmid encoding both FSP27 and DsRed2 (pIRES2-DsRed2-FSP27). (B) COS cells transfected with pIRES2-DsRed2-FSP27 as in A were incubated with 400 μM oleic acid for 24 hours and then stained with Bodipy 493/503 (for TAG). A merged image of Bodipy 493/503 and DsRed2 fluorescence is shown. Arrowheads and arrows indicate cells positive or negative for FSP27 expression, respectively. Original magnification, ×630. (C–E) Quantitation of mean droplet size (C), droplet number (D), and total lipid amount (E) per cell for COS cells treated as in B but also stained with Hoechst 33258 (for nuclei). Total lipid amount was calculated as the product of the area and green fluorescence density of each droplet per cell. Data are mean ± SEM of values from 1,502 and 444 cells negative or positive for DsRed2 fluorescence, respectively, and are expressed relative to the corresponding value for DsRed2-negative cells. *P < 0.001 versus DsRed2-negative cells.