Decreased visceral adiposity accounts for leptin effect on hepatic but notperipheral insulin action

Leptin decreases visceral fat (VF) and Increases peripheral and hepatic ins ulin action. Here, we generated similar decreases in VF using leptin (Lep), beta(3)-adrenoreceptor agonism (beta 3), or food restriction (FR) and aske d whether insulin action would be equally improved. For 8 days before the i n vivo study, Sprague-Dawley rats (n = 24) were either fed ad libitum [cont rol (Con)], treated with Lep or beta 3 (CL-316,243) by implanted osmotic mi ni-pumps, or treated with FR. Total VF was similarly decreased in the latte r three groups (Lep, 3.11 +/- 0.96 g; beta 3, 2.87 +/- 0.48 g; and FR, 3.54 +/- 0.77 g compared with 6.91 +/- 1.41 g in Con; P < 0.001) independent of total fat mass (by (H2O)-H-3) and food intake. Insulin (3 mU.kg(-1).min(-1 )) clamp studies were performed to assess hepatic and peripheral insulin se nsitivity. Decreased VF resulted in similar and marked improvements in insu lin action on glucose production (GP) (Lep, 1.19 +/- 0.51; beta 3, 1.46 +/- 0.68; FR, 2.27 +/- 0.71 compared with 6.06 +/- 0.70 mg.kg(-1).min(-1) in C on; P < 0.001). By contrast, reduction in VF by beta 3 and FR failed to rep roduce the stimulation of insulin-mediated glucose uptake (similar to 60%), glycogen synthesis (similar to 80%), and glycolysis (similar to 25%) obser ved with Lep. We conclude that 1) a moderate decrease in VF uniformly leads to a marked increase in hepatic insulin action, but 2) the effects of lept in on peripheral insulin action are not due to the associated changes in VF or beta 3 activation.