Impairment of body mass reduction-associated activation of brown/beige adipose tissue in patients with type 2 diabetes mellitus

BACKGROUNDS/OBJECTIVES:The activity of brown/beige adipose tissue is inversely proportional to body adiposity. Studies have shown that obese subjects submitted to distinct approaches aimed at reducing body mass present an increase of brown/beige adipose tissue activation. However, it is unknown if this beneficial effect of body mass reduction applies to patients with type 2 diabetes mellitus. In this study, we evaluated the impact of massive body mass reduction obtained as a consequence of bariatric surgery in the cold-induced activation of brown/beige adipose tissue in obese non-diabetic and obese diabetic subjects. SUBJECTS/METHODS:This is an observational study. Fourteen obese non-diabetic, fourteen obese diabetic and eleven lean subjects were included in the study. All obese subjects were submitted to Roux-in-Y gastric bypass and measurements were performed before and eight months after surgery. Brown/beige adipose tissue was evaluated by (18F)-FDG PET/CT-scan and determination of signature transcript expression in specimens obtained in biopsies. RESULTS:Before surgery, mean brown/beige adipose tissue activity and the expression of signature transcripts were similar between obese non-diabetic and obese diabetic groups. Eight months after surgery, body mass reduction was similar between the obese groups. Nevertheless, the activity of brown/beige adipose tissue was increased in obese non-diabetic and unchanged in obese diabetic subjects. This effect was correlated with a more pronounced improvement of insulin resistance, as evaluated by the hyperinsulinemic, euglycemic clamp, in obese non-diabetic subjects as compared with obese diabetic subjects. CONCLUSIONS:Body mass reduction has a more efficient effect to induce the activation of brown/beige adipose tissue in non-diabetic than in diabetic subjects. This effect is accompanied by more pronounced insulin sensitivity and serine 473 phosphorylation of Akt in brown/beige adipose tissue of non-diabetic than in diabetic subjects.