Visceral Obesity is Associated with High Levels of Serum Squalene

• Published in: Obesity (Silver Spring, Md.) Vol. 14; no. 7; pp. 1155 - 1163
• Main Authors: Peltola, Paula, Pihlajamäki, Jussi, Koutnikova, Hana, Ruotsalainen, Eija, Salmenniemi, Urpu, Vauhkonen, Ilkka, Kainulainen, Sakari, Gylling, Helena, Miettinen, Tatu A., Auwerx, Johan, Laakso, Markku
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.2006
• Subjects: Abdomen; Adult; Biomarkers - analysis; Body composition; Body Composition - physiology; Body fat; Cholesterol; Cholesterol - biosynthesis; Cholesterol - metabolism; cholesterol synthesis; Diabetes; Diabetes Mellitus, Type 2 - metabolism; Farnesyl-Diphosphate Farnesyltransferase - genetics; Female; Glucose; Glucose Clamp Technique; Humans; Insulin - metabolism; Insulin resistance; Intestinal Absorption; Intra-Abdominal Fat - metabolism; intra‐abdominal obesity; Lipoproteins; Male; Metabolism; Obesity; Obesity - blood; Obesity - etiology; Obesity - metabolism; Polymorphism, Single-Stranded Conformational; Research methodology; Squalene - blood; squalene synthase; Tomography; type 2 diabetes; Finland
• ISSN: 1930-7381; 1930-739X
• DOI: 10.1038/oby.2006.132

Objective: To investigate the impact of visceral obesity on cholesterol metabolism in normoglycemic offspring of patients with type 2 diabetes. Research Methods and Procedures: 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 ≤ 0.027) and negatively with the rates of insulin‐stimulated whole‐body glucose uptake (r = −0.372 to −0.248, p ≤ 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). Discussion: 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.