genetic predisposition for type 2 diabetes, but not for overweightobesity, is associated with a restricted adipogenesis2型糖尿病的遗传倾向,但不是overweightobesity,限制脂肪形成.pdfVIP

Genetic Predisposition for Type 2 Diabetes, but Not for Overweight/Obesity, Is Associated with a Restricted Adipogenesis 1 1 2 2 Peter Arner , Erik Arner , Ann Hammarstedt , Ulf Smith * 1 Department of Medicine, Karolinska Institute at Karolinska Hospital, Huddinge, Stockholm, Sweden, 2 The Lundberg Laboratory for Diabetes Research, Center of Excellence for Metabolic and Cardiovascular Research, Department of Molecular and Clinical Medicine, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden Abstract Background: Development of Type 2 diabetes, like obesity, is promoted by a genetic predisposition. Although several genetic variants have been identified they only account for a small proportion of risk. We have asked if genetic risk is associated with abnormalities in storing excess lipids in the abdominal subcutaneous adipose tissue. Methodology/Principal Findings: We recruited 164 lean and 500 overweight/obese individuals with or without a genetic predisposition for Type 2 diabetes or obesity. Adipose cell size was measured in biopsies from the abdominal adipose tissue as well as insulin sensitivity (HOMA index), HDL-cholesterol and Apo AI and Apo B. 166 additional non-obese individuals with a genetic predisposition for Type 2 diabetes underwent a euglycemic hyperinsulinemic clamp to measure insulin sensitivity. Genetic predisposition for Type 2 diabetes, but not for overweight/obesity, was associated with inappropriate expansion of the adipose cells, reduced insulin sensitivity and a more proatherogenic lipid profile in non-obese individuals. However, obesity per se induced a similar expansion of adipose cells and dysmetabolic state irrespective of genetic predisposition.