Plasma leptin concentrations during extended fasting and graded glucose infusions: Relationships with changes in glucose, insulin, and FFA

Despite numerous studies, the in vivo regulation of plasma leptin levels in response to nutritional factors continues to remain unclear. We investigat ed temporal and dose-response relationships of plasma leptin in response to physiological changes in insulin/glucose. After an overnight fast of 10 h, lean, healthy subjects were investigated for an additional 16 h of either extended fasting or one of three levels of glycemia/ insulinemia induced by stepwise increasing iv glucose infusions. During extended fasting, plasma leptin values declined steadily and significantly. Plasma leptin levels rem ained constant at glucose concentrations between 5.8-6.5 mmol/liter, which maintained normoinsulinemia at 41.5-45.4 pmol/liter and FFA at 106-123 mg/l iter, but leptin concentrations were increased at higher rates of glucose i nfusion (with plasma glucose rising to 8.7 mmol/liter). Concentrations of s erum leptin were inversely related to FFA levels during extended fasting an d at all levels of glycemia. Our data indicate that in lean healthy subject s, physiological changes in glycemia and insulinemia significantly alter pl asma FFA and leptin concentrations. The increases in leptin concentrations demonstrate close-dependent relationships that appear to relate to changes in FFA levels as well as to changes in glycemia/insulinemia.