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 2

Glucose and energy metabolism in FSP27-knockout mice.

Options: View larger image (or click on image) Download as PowerPoint
Glucose and energy metabolism in FSP27-knockout mice. (A) Body weight of...
(A) Body weight of wild-type, FSP27 heterozygous knockout (+/–), and FSP27-KO (–/–) mice maintained on a standard diet (SD) or fed a high-fat diet (HFD). Data are mean ± SEM (n = 7–11). §P < 0.05 versus corresponding values for wild-type or FSP27 heterozygous knockout mice on the high-fat diet; #P < 0.05 versus corresponding value for FSP27 heterozygous knockout mice on the high-fat diet. (B) Plasma glucose concentrations during an intraperitoneal glucose tolerance test (left panel) or an insulin tolerance test (right panel) in 12-week-old wild-type and FSP27-KO (KO) mice, either maintained on a standard diet or fed a high-fat diet from 4 weeks of age. Data are mean ± SEM (n = 11 for standard diet; n = 8 for high-fat diet.). *P < 0.05, **P < 0.01 versus corresponding value for wild-type animals on the standard diet; †P < 0.05, ††P < 0.01 versus corresponding value for wild-type animals on the high-fat diet. (C) Hyperinsulinemic-euglycemic clamp analysis in 10- to 12-week-old wild-type and FSP27-KO mice fed a high-fat diet. GIR, glucose infusion rate; Rd, rate of glucose disappearance; BHGP, basal hepatic glucose production; CHGP, hepatic glucose production during the clamp period. Data are mean ± SEM (n = 6). §§P < 0.05, ##P < 0.01 versus corresponding value for wild type. (D and E) Whole-body oxygen consumption rate (VO2, expressed in milliliters per minute per gram of body weight) during a 12-hour dark/12-hour light cycle in 12-week-old mice fed a standard diet (n = 3 for wild type; n = 5 for FSP27-KO) (D) or a high-fat diet (n = 6) (E) is shown in the left panels. The average values for the 24-hour period are shown in the right panels. Data are mean ± SEM. ‡P < 0.05, ‡‡P < 0.01 versus wild type. (F and G) Average values of respiratory quotient (VCO2/VO2) (F) and energy expenditure (G) for the 24-hour period in the experiments shown in D and E. Data are mean ± SEM. ‡P < 0.05, ‡‡P < 0.01 versus wild type.