FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets
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
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
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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 PPARĪ³ 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

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Figure 3

Characterization of adipose tissue in FSP27 knockout mice.

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Characterization of adipose tissue in FSP27 knockout mice. (A) Compariso...
(A) Comparison of interscapular brown fat pads (BAT) and epididymal white fat pads (WAT) of 14-week-old wild-type and FSP27-KO mice (left panel). Weights of epididymal WAT, subcutaneous WAT, and BAT isolated from 14-week-old wild-type and FSP27-KO mice (right panels). Data are mean ± SEM (n = 4–8). †P < 0.05 versus the corresponding value for wild type. (B) Sections of subcutaneous WAT and interscapular BAT from 14-week-old wild-type and FSP27-KO mice were stained with hematoxylin-eosin and examined by light microscopy. Scale bar: 20 μm. (C) Transmission electron microscopy of subcutaneous WAT and interscapular BAT from 6-week-old wild-type and FSP27-KO mice. L, lipid droplet; *, mitochondria. Scale bar: 500 nm. (D) Mitochondrial number (left panel) and size (right panel) in subcutaneous WAT, epididymal WAT, and interscapular BAT determined from electron micrographs similar to those in C. Mitochondrial number is expressed per nucleus and was determined for 25 wild-type and 28 FSP27-KO cells for subcutaneous WAT, 33 cells for epididymal WAT, and 56 wild-type and 64 FSP27-KO cells for BAT. Mitochondrial diameter was measured with a scale of 25 nm in 120 cells. Data are mean ± SEM. ††P < 0.01 versus the corresponding value for wild type. (E) Southern blot analysis of total cellular DNA from BAT or WAT of 9-week-old wild-type or FSP27-KO mice with probes specific for the mitochondrial COXI gene and the nuclear 36B4 gene.