Leptin alters metabolic rates before acquisition of its anorectic effect in developing neonatal mice

Leptin inhibits food intake and increases metabolic rates in adult mice. Ne onatal mice need to maximize food intake and also maintain high thermoregul atory metabolic rates to optimize survival, suggesting that leptin may func tion differentially in neonatal versus adult animals. The efficacy of exoge nous leptin to alter these two physiological functions during development w as thus examined in C57BL/6J lean(+/+ or ob/+) and ob/ob (leptin-deficient) mice. Intraperitoneal leptin administration (1 mg/kg body wt) to lean and ob/ob pups from 7 to 10 days of age did not affect milk intake, oxygen cons umption, body weight, or epididymal fat pad weights. Intracerebroventricula r injection of 1 mu g leptin to g-day-old pups also failed to influence mil k intake or oxygen consumption. Because neither lean nor ob/ob pups respond ed to exogenous leptin, high endogenous plasma leptin concentrations per se in these lean mice do not explain their resistance to leptin. Leptin admin istered intracerebroventricularly also failed to alter milk/food intakes of 17-day-old pups but markedly increased oxygen consumption of these older m ice. By 28 days of age, intracerebroventricular leptin inhibited food intak e. The well-defined actions of leptin to reduce food intake and enhance met abolic rates do not develop synchronously. The ability of leptin to acceler ate metabolic rates is acquired early in life and independent of its anorec tic action, which may promote survival of neonates.