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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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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
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cited_by cdi_FETCH-LOGICAL-c562t-67b81f6f500b223986338014462956d9a096f9e5ef796093a18493f7e718fa813
cites cdi_FETCH-LOGICAL-c562t-67b81f6f500b223986338014462956d9a096f9e5ef796093a18493f7e718fa813
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container_issue 8
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container_title The Journal of clinical investigation
container_volume 118
creator 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
description 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.
doi_str_mv 10.1172/jci34090
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Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Biological Sciences</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nishino, Naonobu</au><au>Tamori, Yoshikazu</au><au>Tateya, Sanshiro</au><au>Kawaguchi, Takayuki</au><au>Shibakusa, Tetsuro</au><au>Mizunoya, Wataru</au><au>Inoue, Kazuo</au><au>Kitazawa, Riko</au><au>Kitazawa, Sohei</au><au>Matsuki, Yasushi</au><au>Hiramatsu, Ryuji</au><au>Masubuchi, Satoru</au><au>Omachi, Asako</au><au>Kimura, Kazuhiro</au><au>Saito, Masayuki</au><au>Amo, Taku</au><au>Ohta, Shigeo</au><au>Yamaguchi, Tomohiro</au><au>Osumi, Takashi</au><au>Cheng, Jinglei</au><au>Fujimoto, Toyoshi</au><au>Nakao, Harumi</au><au>Nakao, Kazuki</au><au>Aiba, Atsu</au><au>Okamura, Hitoshi</au><au>Fushiki, Tohru</au><au>Kasuga, Masato</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>2008-08-01</date><risdate>2008</risdate><volume>118</volume><issue>8</issue><spage>2808</spage><epage>2821</epage><pages>2808-2821</pages><issn>0021-9738</issn><eissn>1558-8238</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><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 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.</abstract><cop>United States</cop><pub>American Society for Clinical Investigation</pub><pmid>18654663</pmid><doi>10.1172/jci34090</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record>
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ispartof The Journal of clinical investigation, 2008-08, Vol.118 (8), p.2808-2821
issn 0021-9738
1558-8238
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2483680
source PubMed Central(OpenAccess); Free E-Journal (出版社公開部分のみ)
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
title FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets
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