Key enzyme in leptin-induced anorexia

Leptin is a key hormonal regulator of energy balance that acts upon hypothalamic neurons to reduce food intake, but the intracellular mechanisms involved are incompletely understood. Here we show that systemic administration of leptin in rats activates the enzyme phosphatidylinositol-3-OH kinase (PI(3)K) in the hypothalamus and that intracerebroventricular (i.c.v.) infusion of inhibitors of this enzyme prevents leptin-induced anorexia. Our results indicate that PI(3)K is a crucial enzyme in the signal-transduction pathway that links hypothalamic leptin to reduced food intake.