title: Hepatic steatosis in leptin-deficient mice is promoted by the PPARgamma target gene Fsp27.
abstract: Peroxisome proliferator-activated receptor gamma (PPARgamma) is induced in leptin-deficient (ob/ob) mouse liver and is critical for the development of hepatic steatosis. The present study shows that fat-specific protein 27 (Fsp27) in ob/ob liver is a direct target gene of PPARgamma and can elevate hepatic triglyceride levels. FSP27 belongs to the CIDE family, composed of CIDE A, CIDE B, and FSP27/CIDE C, all of which contain a conserved CIDE-N domain. FSP27 was recently reported to be a lipid droplet-binding protein and to promote lipid accumulation in adipocytes. The Fsp27 gene was expressed at high levels in ob/ob liver and at markedly lower levels in ob/ob livers lacking PPARgamma. Forced expression of FSP27 by adenovirus in hepatocytes in vitro or in vivo led to increased triglyceride levels. Knockdown by adenovirus expressing FSP27 shRNA resulted in lower accumulation of hepatic triglycerides compared to control adenovirus-infected liver. Taken together, these results indicate that FSP27 is a direct mediator of PPARgamma-dependent hepatic steatosis.
authors.affiliation: Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. matsusuk@fukuoka-u.ac.jp
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Matsusue
authors.forename: Takashi
authors.initials: T
authors.lastname: Kusakabe
authors.forename: Takahiro
authors.initials: T
authors.lastname: Noguchi
authors.forename: Shouichi
authors.initials: S
authors.lastname: Takiguchi
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Suzuki
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamano
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000378:metabolism; D020738:Leptin / Q000172:deficiency* / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C112510:Cidea protein, mouse; D020738:Leptin; D047495:PPAR gamma; D011506:Proteins; D014280:Triglycerides; C525805:fat-specific protein 27, mouse; D012313:RNA