title: Fatty liver and obesity: phenotypically correlated but genetically distinct traits in a mouse model of type 2 diabetes.
abstract: OBJECTIVE
  Obesity and fatty liver are commonly associated with type 2 diabetes, but the genetic and functional bases linking fatty liver with obesity and diabetes are largely unknown. Our aim was to investigate the association of fatty liver with obesity and other diabetes-related phenotypes and to define the genetic control of obesity and fatty liver.
  
  
  METHODS
  We established 306 F2 mice by crossing Nagoya-Shibata-Yasuda (NSY) mice, an animal model of type 2 diabetes, with control C3H mice, and analysed their phenotypes. Whole-genome screening of F2 mice was performed to identify the loci responsible for fatty liver and obesity.
  
  
  RESULTS
  A strong association of fatty liver with obesity, hyperinsulinaemia and hyperglycaemia was observed in F2 mice. Using whole-genome screening in 306 F2 mice, we mapped a new locus for fatty liver (Fl1n) on chromosome 6 (maximum logarithm of odds score [MLS] 10.0) and one for body weight (Bw1n) on chromosome 7 (MLS 5.1). Fl1n was linked to epididymal fat weight as well as fatty liver, but its effects were opposite in the two tissues in that the NSY allele increased liver fat but decreased epididymal fat, suggesting a role of Fl1n in partitioning of fat mass. The sequence of peroxisome proliferator-activated receptor gamma (Pparg), a candidate for Fl1n, showed allelic variation between NSY and C3H mice.
  
  
  CONCLUSIONS
  These data suggest that fatty liver and obesity are phenotypically related but genetically independent. Loci homologous to Fl1n and Bw1n are good candidate genes for susceptibility to fatty liver and obesity in humans.
authors.affiliation: Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Itoi-Babaya
authors.forename: H
authors.initials: H
authors.lastname: Ikegami
authors.forename: T
authors.initials: T
authors.lastname: Fujisawa
authors.forename: H
authors.initials: H
authors.lastname: Ueda
authors.forename: K
authors.initials: K
authors.lastname: Nojima
authors.forename: N
authors.initials: N
authors.lastname: Babaya
authors.forename: M
authors.initials: M
authors.lastname: Kobayashi
authors.forename: S
authors.initials: S
authors.lastname: Noso
authors.forename: Y
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: K
authors.initials: K
authors.lastname: Yamaji
authors.forename: M
authors.initials: M
authors.lastname: Shibata
authors.forename: T
authors.initials: T
authors.lastname: Ogihara
mesh_terms: D000818:Animals; D015992:Body Mass Index; D033481:Chromosomes, Mammalian / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000235:genetics*; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D040641:Quantitative Trait Loci / Q000235:genetics