title: Adipocyte size is associated with NAFLD independent of obesity, fat distribution, and PNPLA3 genotype.
abstract: OBJECTIVE
  Adipocyte hypertrophy has been suggested to be causally linked with inflammation and systemic insulin resistance. The aim of the study was to determine whether increased adipocyte size is associated with increased liver fat content due to nonalcoholic fatty liver disease (NAFLD) in humans independent of obesity, fat distribution and genetic variation in the patatin-like phospholipase domain-containing 3 gene (PNPLA3; adiponutrin) at rs738409.
  
  
  METHODS
  One hundred nineteen non-diabetic subjects in a cross-sectional study with a median age of 39 years, mean ± SD BMI of 30.0 ± 5.7 kg m(-2) were studied. Abdominal subcutaneous (SC) adipocyte size, liver fat [proton magnetic resonance spectroscopy ((1) H-MRS)], intra-abdominal (IA), and abdominal SC adipose tissue volumes [magnetic resonance imaging (MRI)] and the PNPLA3 genotype at rs738409 were determined. Univariate and multiple linear regression analysis were used to identify independent predictors of liver fat content.
  
  
  RESULTS
  In multiple linear regression analysis, age, gender, BMI, the IA/SC ratio, and PNPLA3 genotype explained 42% of variation in liver fat content. Addition of adipocyte size (P < 0.0001) to the model increased the percent of explanation to 53%. Thus, 21% of known variation in liver fat could be explained by adipocyte size alone.
  
  
  CONCLUSIONS
  Increased adipocyte size highly significantly contributes to liver fat accumulation independent of other causes.
authors.affiliation: Minerva Foundation Institute for Medical Research, Helsinki, Finland. elina.petaja@helsinki.fi
authors.forename: Elina M
authors.initials: EM
authors.lastname: Petäjä
authors.forename: Ksenia
authors.initials: K
authors.lastname: Sevastianova
authors.forename: Antti
authors.initials: A
authors.lastname: Hakkarainen
authors.forename: Marju
authors.initials: M
authors.lastname: Orho-Melander
authors.forename: Nina
authors.initials: N
authors.lastname: Lundbom
authors.forename: Hannele
authors.initials: H
authors.lastname: Yki-Järvinen
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D000328:Adult; D001823:Body Composition; D050218:Body Fat Distribution; D003430:Cross-Sectional Studies; D005234:Fatty Liver / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance; D008049:Lipase / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000503:physiopathology*; D009929:Organ Size; D050507:Subcutaneous Fat, Abdominal / Q000503:physiopathology; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent