Acute effect of leptin on hepatic glycogenolysis and gluconeogenesis in perfused rat liver

Leptin circulates in blood and is involved in body weight control primarily via hypothalamic receptors. To examine its direct metabolic action, effect s of short-term portal leptin infusion: 1) on postprandial basal and epinep hrine-stimulated glycogenolysis; and 2) on postabsorptive lactate-stimulate d gluconeogenesis were studied in isolated perfused rat livers. Incremental epinephrine (150 pmol . min(-1) . g(-1) liver)-stimulated glucose release (in mu mol/g liver within 30 minutes; control: 28.3 +/- 2.8) was suppressed (P < .05) kby 44% (15.8 +/- 1.6), by 48% (14.6 +/- 4.1), and by 53% (13.3 +/- 2.1) during insulin (3 pmol . min(-1) . g(-1) liver), leptin (30 pmol . min(-1) . g(-1) liver), and simultaneous leptin + insulin infusion. Perfus ate cyclic adenosine monophosphate increased approximately twofold during e pinephrine stimulation in all groups. Neither leptin nor insulin affected h epatic lactate production, bile flow, or portal pressure in the fed state. In the postabsorptive state (20-hour fasting), rates of lactate (10 mmol/L) -dependent hepatic glucose release (in mu mol. min(-1) . g(-1) liver; contr ol: 0.12 +/- 0.01) were increased (P < .01) to 0.35 +/- 0.02 and to 0.24 +/ - 0.01 by glucagon (3 pmol . min(-1) . g(-1) liver) and by leptin (15 pmol . min(-1) . g(-1) liver), respectively. In parallel, lactate uptake rates ( in mu mol . min(-1) . g(-1) liver) were higher in the presence of both gluc agon (0.90 +/- 0.03) and leptin (0.84 +/- 0.02) compared with control (0.68 +/- 0.04). In conclusion, leptin modulates hepatic glucose fluxes and may contribute to direct humoral regulation of liver glycogen stores in the fas ted as well as in the fed state.