title: Visceral obesity is associated with high levels of serum squalene.
abstract: OBJECTIVE
  To investigate the impact of visceral obesity on cholesterol metabolism in normoglycemic offspring of patients with type 2 diabetes.
  
  
  METHODS
  The proportion of intra-abdominal fat (IAF) was measured by abdominal computer tomography, and serum cholesterol synthesis and absorption markers were determined by gas-liquid chromatography in 109 normoglycemic offspring of patients with type 2 diabetes. Insulin action was measured with the hyperinsulinemic euglycemic clamp. The gene encoding squalene synthase (farnesyl-diphosphate farnesyltransferase 1) was screened with the single-strand conformation polymorphism analysis and direct sequencing.
  
  
  RESULTS
  Cholesterol synthesis markers correlated positively with IAF (r = 0.213 to 0.309, p < or = 0.027) and negatively with the rates of insulin-stimulated whole-body glucose uptake (r = -0.372 to -0.248, p < or = 0.010). However, serum squalene, the first measured precursor of cholesterol synthesis, showed a positive correlation with IAF (r = 0.309, p = 0.001) without any association with subcutaneous fat or insulin sensitivity. Variation in the farnesyl-diphosphate farnesyltransferase 1 gene did not explain elevated serum squalene levels in viscerally obese subjects. From the cholesterol absorption markers, cholestanol was associated negatively with IAF and positively with whole-body glucose uptake (p < 0.05).
  
  
  CONCLUSIONS
  High serum squalene levels are associated with visceral obesity but not with subcutaneous obesity. Whether this finding is causally connected to visceral obesity remains to be established.
authors.affiliation: Department of Medicine, University of Kuopio, Kuopio, Finland.
authors.forename: Paula
authors.initials: P
authors.lastname: Peltola
authors.forename: Jussi
authors.initials: J
authors.lastname: Pihlajamäki
authors.forename: Hana
authors.initials: H
authors.lastname: Koutnikova
authors.forename: Eija
authors.initials: E
authors.lastname: Ruotsalainen
authors.forename: Urpu
authors.initials: U
authors.lastname: Salmenniemi
authors.forename: Ilkka
authors.initials: I
authors.lastname: Vauhkonen
authors.forename: Sakari
authors.initials: S
authors.lastname: Kainulainen
authors.forename: Helena
authors.initials: H
authors.lastname: Gylling
authors.forename: Tatu A
authors.initials: TA
authors.lastname: Miettinen
authors.forename: Johan
authors.initials: J
authors.lastname: Auwerx
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001823:Body Composition / Q000502:physiology; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000235:genetics*; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007408:Intestinal Absorption; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000097:blood / Q000209:etiology* / Q000378:metabolism; D018807:Polymorphism, Single-Stranded Conformational; D013185:Squalene / Q000097:blood*
chemical_list: D015415:Biomarkers; D007328:Insulin; D013185:Squalene; D002784:Cholesterol; D013186:Farnesyl-Diphosphate Farnesyltransferase