title: SLC25A24 as a novel susceptibility gene for low fat mass in humans and mice.
abstract: BACKGROUND
  Genetic factors contribute to the development of obesity.
  
  
  OBJECTIVE
  The aim of this study was to identify novel genes that regulate body fat mass.
  
  
  METHODS
  We performed a search for single nucleotide polymorphisms (SNPs) associated with body fat percentage using SNP arrays and undertook a replication study and animal study.
  
  
  METHODS
  Baseline examinations were conducted in 251 (first-stage analysis), 499 (second-stage analysis), and 732 (additional analyses) Japanese postmenopausal women. The mean age (mean ± SD) of the subjects was 66.5 ± 9.4 years. We also analyzed the fat-related phenotypes of a candidate gene in knockout mice.
  
  
  RESULTS
  In the analysis of total body fat, we focused on an SNP of SLC25A24 that showed the lowest significant P value obtained from multiple comparison tests among Japanese postmenopausal women. A significant association was also found between SLC25A24 SNPs and body mass index in the 1482 Japanese postmenopausal women examined in the study. The SLC25A24 SNPs affected the mRNA expression of SLC25A24 in human preadipocytes. Compared with wild-type mice, Slc25a24-KO mice had significantly lower body weights and white adipose tissue weights. Adipocyte differentiation was inhibited in Slc25a24-KO adipose tissues and Slc25a24-knockdown adipocytes.
  
  
  CONCLUSIONS
  Genetic analyses in human and mouse models revealed the importance of SLC25A24/Slc25a24 in the regulation of body fat mass and adipogenesis.
authors.affiliation: Departments of Geriatric Medicine (T.U., N.S., Y.O., S.I.) and Anti-Aging Medicine (T.U., N.S., S.I.), Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; and Research Institute and Practice for Involutional Diseases (M.S.), Nagano 399-8101, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Urano
authors.forename: Masataka
authors.initials: M
authors.lastname: Shiraki
authors.forename: Noriko
authors.initials: N
authors.lastname: Sasaki
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Ouchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000235:genetics; D000273:Adipose Tissue / Q000378:metabolism*; D050154:Adiposity / Q000235:genetics*; D000368:Aged; D000818:Animals; D017920:Antiporters / Q000235:genetics / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000502:physiology*; D009765:Obesity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D017920:Antiporters; D002135:Calcium-Binding Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; C579318:SCaMC-1like protein, mouse; C487500:SLC25A24 protein, human