Developmental and food-access-dependent changes in effector systems activated by leptin

In small mammals leptin reduces fat stores not only by inhibiting food intake but also by disinhibiting metabolic cold defense. Presuming that postnatal age and feeding regime set the conditions for either mode of leptin action, we compared the caloric equivalents of changes in fat mass, metabolic rate (MR) and food intake (FI) induced by 10-day treatments with leptin, in rats treated from postnatal days 7, 15, 25 onward and in adult mice that were free-feeding or food restricted. Whereas MR changes are known to dominate from postnatal days 7-16, changes in MR explained only about 50% and 30% of the leptin-induced changes in fat mass between days 15-24 and days 25-34, respectively. In adult mice of similar body weights, leptin-induced reductions in fat mass under free-feeding conditions were due only to FI decreases but due only to MR increases under food-restricted conditions. Thus, the same leptin treatment induces the same percentage decrease in body fat content by driving the two effectors differently, depending on age and feeding conditions. Consequently, in assessing the effects of leptin under various physiological conditions, short-term measurements of FI or MR alone are not sufficient. Instead, determination of the resultant decreases in total body fat is required.