Improvement in insulin sensitivity by weight loss does not affect hyperinsulinemia-mediated reduction in total and...

Acute hyperinsulinemia reduces total and high molecular weight (HMW) adiponectin levels in humans. Whether an increase in insulin sensitivity (IS) is accompanied by a greater suppressive effect of hyperinsulinemia on adiponectin levels is unknown, however. To clarify the inhibitory role of insulin on adiponectin, total and HMW adiponectin levels were measured during acute hyperinsulinemia before and after an improvement in insulin sensitivity in response to weight loss. Forty-six overweight and obese postmenopausal women were randomized to either 6-month caloric restriction (CR) alone (n = 22), or CR with resistance training (CR+RT, n = 24). IS (hyperinsulinemic-euglycemic clamp) was assessed before and after weight loss. Total and HMW adiponectin levels were measured by ELISA at baseline, 90, 160, and 180 min of each clamp. Relative mean body weight loss was -8.0% ± 4.4% for both groups (CR: -7.7% ± 3.8%; CR+RT: -8.2% ± 5.0%). IS increased significantly, by 18.4% ± 25.3% (CR: 19.3% ± 29.7%; CR+RT: 17.7% ± 21.0%). Before each intervention, total and HMW adiponectin levels in both groups significantly decreased in response to hyperinsulinemia (total: -8.4% ± 19.4%; HMW: -3.2% ± 13.2%). Despite the improvement in IS seen after each intervention, a similar pattern of reduction to that before weight loss was observed in total and HMW adiponectin levels during hyperinsulinemia. These results establish that total and HMW adiponectin levels decline during a hyperinsulinemic-euglycemic clamp. Also, the insulin-sensitizing effect of weight loss via caloric restriction alone or with resistance training does not amplify the reduction in adiponectin levels observed during hyperinsulinemia in healthy postmenopausal women.