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

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 PPARgamma in 3T3-L1 cells and performed a microarray screen. The fat-specific protein...

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Bibliographic Details
Published in:The Journal of clinical investigation 2008-08, Vol.118 (8), p.2808-2821
Main Authors: Nishino, Naonobu, Tamori, Yoshikazu, Tateya, Sanshiro, Kawaguchi, Takayuki, Shibakusa, Tetsuro, Mizunoya, Wataru, Inoue, Kazuo, Kitazawa, Riko, Kitazawa, Sohei, Matsuki, Yasushi, Hiramatsu, Ryuji, Masubuchi, Satoru, Omachi, Asako, Kimura, Kazuhiro, Saito, Masayuki, Amo, Taku, Ohta, Shigeo, Yamaguchi, Tomohiro, Osumi, Takashi, Cheng, Jinglei, Fujimoto, Toyoshi, Nakao, Harumi, Nakao, Kazuki, Aiba, Atsu, Okamura, Hitoshi, Fushiki, Tohru, Kasuga, Masato
Format: Article
Language:English
Subjects:
3T3-L1 Cells
Adenoviruses
Adipocytes
Adipocytes - cytology
Adipocytes - metabolism
Adipose Tissue, Brown - cytology
Adipose Tissue, Brown - metabolism
Adipose Tissue, Brown - ultrastructure
Adipose Tissue, White - cytology
Adipose Tissue, White - metabolism
Adipose Tissue, White - ultrastructure
Animals
Biomedical research
Body fat
Cells, Cultured
Cercopithecus aethiops
Control
COS Cells
Crosses, Genetic
Cytoplasm
Dehydrogenases
Energy Metabolism - physiology
Energy storage
Fat cells
Gene Expression Regulation
Genetic aspects
Heterozygote
Insulin resistance
Lipids
Lipolysis - physiology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Mutant Strains
Molecular Weight
Obesity
Physiological aspects
Proteins
Proteins - chemistry
Proteins - genetics
Proteins - metabolism
Risk factors
RNA, Small Interfering - metabolism
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Summary: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 PPARgamma 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.
ISSN:0021-9738
1558-8238
DOI:10.1172/jci34090