title: Adipocyte-specific disruption of fat-specific protein 27 causes hepatosteatosis and insulin resistance in high-fat diet-fed mice.
abstract: White adipose tissue (WAT) functions as an energy reservoir where excess circulating fatty acids are transported to WAT, converted to triglycerides, and stored as unilocular lipid droplets. Fat-specific protein 27 (FSP27, CIDEC in humans) is a lipid-coating protein highly expressed in mature white adipocytes that contributes to unilocular lipid droplet formation. However, the influence of FSP27 in adipose tissue on whole-body energy homeostasis remains unclear. Mice with adipocyte-specific disruption of the Fsp27 gene (Fsp27(ΔAd)) were generated using an aP2-Cre transgene with the Cre/LoxP system. Upon high-fat diet feeding, Fsp27(ΔAd) mice were resistant to weight gain. In the small WAT of these mice, small adipocytes containing multilocular lipid droplets were dispersed. The expression levels of the genes associated with mitochondrial abundance and brown adipocyte identity were increased, and basal lipolytic activities were significantly augmented in adipocytes isolated from Fsp27(ΔAd) mice compared with the Fsp27(F/F) counterparts. The impaired fat-storing function in Fsp27(ΔAd) adipocytes and the resultant lipid overflow from WAT led to marked hepatosteatosis, dyslipidemia, and systemic insulin resistance in high-fat diet-treated Fsp27(ΔAd) mice. These results demonstrate a critical role for FSP27 in the storage of excess fat in WAT with minimizing ectopic fat accumulation that causes insulin-resistant diabetes and non-alcoholic fatty liver disease. This mouse model may be useful for understanding the significance of fat-storing properties of white adipocytes and the role of local FSP27 in whole-body metabolism and estimating the pathogenesis of human partial lipodystrophy caused by CIDEC mutations.
authors.affiliation: From the Laboratory of Metabolism, Center for Cancer Research, NCI, National Institutes of Health and.
authors.forename: Naoki
authors.initials: N
authors.lastname: Tanaka
authors.affiliation: From the Laboratory of Metabolism, Center for Cancer Research, NCI, National Institutes of Health and.
authors.forename: Shogo
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: From the Laboratory of Metabolism, Center for Cancer Research, NCI, National Institutes of Health and.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Matsubara
authors.affiliation: From the Laboratory of Metabolism, Center for Cancer Research, NCI, National Institutes of Health and.
authors.forename: Changtao
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Molecular Signaling Section and.
authors.forename: Wataru
authors.initials: W
authors.lastname: Sakamoto
authors.affiliation: Mouse Metabolism Core Laboratory, NIDDK, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Chanturiya
authors.affiliation: Mouse Metabolism Core Laboratory, NIDDK, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Ruifeng
authors.initials: R
authors.lastname: Teng
authors.affiliation: Mouse Metabolism Core Laboratory, NIDDK, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Oksana
authors.initials: O
authors.lastname: Gavrilova
authors.affiliation: From the Laboratory of Metabolism, Center for Cancer Research, NCI, National Institutes of Health and gonzalef@mail.nih.gov.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D011506:Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D011506:Proteins; C525805:fat-specific protein 27, mouse
keywords: Adipose Tissue; Diabetes; Hepatocyte; Insulin Resistance; Lipid; Mouse