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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 |
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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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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.</description><identifier>ISSN: 0021-9738</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/jci34090</identifier><identifier>PMID: 18654663</identifier><language>eng</language><publisher>United States: American Society for Clinical Investigation</publisher><subject>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</subject><ispartof>The Journal of clinical investigation, 2008-08, Vol.118 (8), p.2808-2821</ispartof><rights>COPYRIGHT 2008 American Society for Clinical Investigation</rights><rights>Copyright American Society for Clinical Investigation Aug 2008</rights><rights>Copyright © 2008, American Society for Clinical Investigation 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c562t-67b81f6f500b223986338014462956d9a096f9e5ef796093a18493f7e718fa813</citedby><cites>FETCH-LOGICAL-c562t-67b81f6f500b223986338014462956d9a096f9e5ef796093a18493f7e718fa813</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483680/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483680/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,733,786,790,891,27957,27958,53827,53829</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18654663$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nishino, Naonobu</creatorcontrib><creatorcontrib>Tamori, Yoshikazu</creatorcontrib><creatorcontrib>Tateya, Sanshiro</creatorcontrib><creatorcontrib>Kawaguchi, Takayuki</creatorcontrib><creatorcontrib>Shibakusa, Tetsuro</creatorcontrib><creatorcontrib>Mizunoya, Wataru</creatorcontrib><creatorcontrib>Inoue, Kazuo</creatorcontrib><creatorcontrib>Kitazawa, Riko</creatorcontrib><creatorcontrib>Kitazawa, Sohei</creatorcontrib><creatorcontrib>Matsuki, Yasushi</creatorcontrib><creatorcontrib>Hiramatsu, Ryuji</creatorcontrib><creatorcontrib>Masubuchi, Satoru</creatorcontrib><creatorcontrib>Omachi, Asako</creatorcontrib><creatorcontrib>Kimura, Kazuhiro</creatorcontrib><creatorcontrib>Saito, Masayuki</creatorcontrib><creatorcontrib>Amo, Taku</creatorcontrib><creatorcontrib>Ohta, Shigeo</creatorcontrib><creatorcontrib>Yamaguchi, Tomohiro</creatorcontrib><creatorcontrib>Osumi, Takashi</creatorcontrib><creatorcontrib>Cheng, Jinglei</creatorcontrib><creatorcontrib>Fujimoto, Toyoshi</creatorcontrib><creatorcontrib>Nakao, Harumi</creatorcontrib><creatorcontrib>Nakao, Kazuki</creatorcontrib><creatorcontrib>Aiba, Atsu</creatorcontrib><creatorcontrib>Okamura, Hitoshi</creatorcontrib><creatorcontrib>Fushiki, Tohru</creatorcontrib><creatorcontrib>Kasuga, Masato</creatorcontrib><title>FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><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.</description><subject>3T3-L1 Cells</subject><subject>Adenoviruses</subject><subject>Adipocytes</subject><subject>Adipocytes - cytology</subject><subject>Adipocytes - metabolism</subject><subject>Adipose Tissue, Brown - cytology</subject><subject>Adipose Tissue, Brown - metabolism</subject><subject>Adipose Tissue, Brown - ultrastructure</subject><subject>Adipose Tissue, White - cytology</subject><subject>Adipose Tissue, White - metabolism</subject><subject>Adipose Tissue, White - ultrastructure</subject><subject>Animals</subject><subject>Biomedical research</subject><subject>Body fat</subject><subject>Cells, Cultured</subject><subject>Cercopithecus aethiops</subject><subject>Control</subject><subject>COS Cells</subject><subject>Crosses, Genetic</subject><subject>Cytoplasm</subject><subject>Dehydrogenases</subject><subject>Energy Metabolism - physiology</subject><subject>Energy storage</subject><subject>Fat cells</subject><subject>Gene Expression Regulation</subject><subject>Genetic aspects</subject><subject>Heterozygote</subject><subject>Insulin resistance</subject><subject>Lipids</subject><subject>Lipolysis - physiology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mice, Mutant Strains</subject><subject>Molecular Weight</subject><subject>Obesity</subject><subject>Physiological aspects</subject><subject>Proteins</subject><subject>Proteins - chemistry</subject><subject>Proteins - genetics</subject><subject>Proteins - metabolism</subject><subject>Risk factors</subject><subject>RNA, Small Interfering - metabolism</subject><issn>0021-9738</issn><issn>1558-8238</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNqF0k1vEzEQBuAVAtFSkPgFyOJQwSHgj7XXviBVEYWgSkUUuFrOZrxx5LW3thfIjZ_OhkTQcOHkg58Z6Z2ZqnpK8CtCGvp60zpWY4XvVaeEczmTlMn71SnGlMxUw-RJ9SjnDcakrnn9sDohUvBaCHZa_by8-Ugb1MZQkluOBTIqEYG1rnUQCoIAqduiXGIyHSAXUD8mFwB9X7sCyKzcENvtrmy5RUOKfSwudKisAdmYelNcDChaNAbnYzt6k5B3g1uhVYqDh5IfVw-s8RmeHN6z6svl28_z97Or63eL-cXVrOWClplolpJYYTnGS0qZkoIxucsjqOJipQxWwirgYBslsGKGyFox20BDpDWSsLPqzb7vMC57WLVTuGS8HpLrTdrqaJw-_glurbv4TdNaMiHx1OD80CDF2xFy0b3LLXhvAsQxa6GYpJizCT7_B27imMIUTlOMOW-kqif0co8640G7sFsA_CidGXPWi5tP-mIKQDGtqfiPvf56bM_v2DUYX9Y5-nG3h3wMX-xhm2LOCeyfURCsd0elP8wXv49qos_uju4vPFwR-wVvG8YJ</recordid><startdate>20080801</startdate><enddate>20080801</enddate><creator>Nishino, Naonobu</creator><creator>Tamori, Yoshikazu</creator><creator>Tateya, Sanshiro</creator><creator>Kawaguchi, Takayuki</creator><creator>Shibakusa, Tetsuro</creator><creator>Mizunoya, Wataru</creator><creator>Inoue, Kazuo</creator><creator>Kitazawa, Riko</creator><creator>Kitazawa, Sohei</creator><creator>Matsuki, Yasushi</creator><creator>Hiramatsu, Ryuji</creator><creator>Masubuchi, Satoru</creator><creator>Omachi, Asako</creator><creator>Kimura, Kazuhiro</creator><creator>Saito, Masayuki</creator><creator>Amo, Taku</creator><creator>Ohta, Shigeo</creator><creator>Yamaguchi, Tomohiro</creator><creator>Osumi, Takashi</creator><creator>Cheng, Jinglei</creator><creator>Fujimoto, Toyoshi</creator><creator>Nakao, Harumi</creator><creator>Nakao, Kazuki</creator><creator>Aiba, Atsu</creator><creator>Okamura, Hitoshi</creator><creator>Fushiki, Tohru</creator><creator>Kasuga, Masato</creator><general>American Society for Clinical Investigation</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>S0X</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20080801</creationdate><title>FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c562t-67b81f6f500b223986338014462956d9a096f9e5ef796093a18493f7e718fa813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>3T3-L1 Cells</topic><topic>Adenoviruses</topic><topic>Adipocytes</topic><topic>Adipocytes - 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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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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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