Calorigenic actions of leptin are additive to, but not dependent on, those of thyroid hormones

Abstract

We examined a possible mechanistic interaction between leptin and thyroid hormones in rats with hypothyroidism induced by thyroidectomy (TX) and propylthiouracil administration. In study 1, the TX rats were treated by vehicle (V, n = 9) or by recombinant murine leptin (L, 0.3 mg · kg−1 · day−1, n = 9) or were pair-fed (PF, n = 9) against L. In study 2, the TX rats were all given 3,3′5′-triiodo-l-thyronine (T3) replacement (T, 5 μg · kg−1 · day−1) to correct hypothyroidism. They were then subdivided into three groups, namely, vehicle (T+V, n = 9), leptin (T+L, n = 10), and pair-feeding (T+PF, n = 9), similar to study 1 except for T3 (T). Reduced food consumption and weight gain in the TX rats were reversed by T3 replacement. Leptin suppressed food intake in the TX rats regardless of T3 replacement. O2consumption (V˙o 2) and CO2production (V˙co 2) were reduced in TX rats ( P < 0.05 vs. normal) but were normalized by either T3 or leptin treatment. T+L additively increasedV˙o 2 andV˙co 2 ( P < 0.05 vs. TX, T3, and L). The respiratory exchange ratio was unaltered in TX rats, with and without T3, but was significantly reduced by L or T+L treatments. These results indicate that the metabolic actions of leptin are not dependent on a normal thyroid status and that the effects of leptin and T3 on oxidative metabolism are additive.