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 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.
Nishino
Naonobu
N
Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Tamori
Yoshikazu
Y
Tateya
Sanshiro
S
Kawaguchi
Takayuki
T
Shibakusa
Tetsuro
T
Mizunoya
Wataru
W
Inoue
Kazuo
K
Kitazawa
Riko
R
Kitazawa
Sohei
S
Matsuki
Yasushi
Y
Hiramatsu
Ryuji
R
Masubuchi
Satoru
S
Omachi
Asako
A
Kimura
Kazuhiro
K
Saito
Masayuki
M
Amo
Taku
T
Ohta
Shigeo
S
Yamaguchi
Tomohiro
T
Osumi
Takashi
T
Cheng
Jinglei
J
Fujimoto
Toyoshi
T
Nakao
Harumi
H
Nakao
Kazuki
K
Aiba
Atsu
A
Okamura
Hitoshi
H
Fushiki
Tohru
T
Kasuga
Masato
M
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D052436:Adipose Tissue, White / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003433:Crosses, Genetic; D004734:Energy Metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D006579:Heterozygote; D008066:Lipolysis / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008970:Molecular Weight; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism
D011506:Proteins; D034741:RNA, Small Interfering; C525805:fat-specific protein 27, mouse