Visceral obesity is associated with high levels of serum squalene.
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.
Peltola
Paula
P
Department of Medicine, University of Kuopio, Kuopio, Finland.
Pihlajamäki
Jussi
J
Koutnikova
Hana
H
Ruotsalainen
Eija
E
Salmenniemi
Urpu
U
Vauhkonen
Ilkka
I
Kainulainen
Sakari
S
Gylling
Helena
H
Miettinen
Tatu A
TA
Auwerx
Johan
J
Laakso
Markku
M
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*
D015415:Biomarkers; D007328:Insulin; D013185:Squalene; D002784:Cholesterol; D013186:Farnesyl-Diphosphate Farnesyltransferase