Inhibition of leptin secretion by insulin and metformin in cultured rat adipose tissue

Leptin's role in the regulation of food intake, energy expenditure and weig ht control are widely recognized, especially in rodents. Likewise, the pote ntial regulation of leptin secretion by insulin (and vice versa) has been o f particular interest insofar as these nutrient signals may have meaningful , even adverse (inter)actions, in diabetes. We used a freshly isolated rat adipose tissue culture model to examine the effect of insulin, metformin an d glibenclamide on basal and steroid-stimulated leptin secretion. This mode l was selected because of its physiologic rates of leptin formation and pre servation of potentially significant cell-cell interactions compared to iso lated cells. The basal rate of leptin secretion was 3.4 +/- 1.2 ng/100 mg t issue/24 h. The addition of 100 nM dexamethasone or 400 nM hydrocortisone s timulated leptin secretion by 3-4 fold over basal (no steroid). Insulin inh ibited both basal and steroid-activated leptin secretion by 35-50%. This in hibition was present with either 1 mM pyruvate or 5 mM glucose as a substra te suggesting that glycolysis was not required. Metformin inhibited basal a nd dexamethasone-stimulated leptin secretion in a dose dependent manner (50 % inhibition occurred at 1 mM metformin) while glibenclamide was ineffectiv e. The effect of insulin on isolated fat cells versus fat tissue was tested in parallel. After 24 h in culture, insulin inhibited leptin secretion sim ilarly in both adipose preparations. The addition of 300 nM (-)N6-(2-phenyl isopropyl)-adenosine did not alter the results. (C) 2000 Elsevier Science B .V. All rights reserved.