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

We examined a possible mechanistic interaction between leptin and thyroid h ormones in rats with hypothyroidism induced by thyroidectomy (TX) and propy lthiouracil 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 (T-3) replacement (T, 5 mug.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 suppres sed food intake in the TX rats regardless of T3 replacement. O-2 consumptio n ((V) over dot o(2)) and CO2 production ((V) over dot CO2) were reduced in TX rats (P< 0.05 vs. normal) but were normalized by either T-3 or leptin t reatment. T+L additively increased (V) over dot O-2 and (V) over dot CO2 (P < 0.05 vs. TX, T-3, and L). The respiratory exchange ratio was unaltered in TX rats, with and without T-3, but was significantly reduced by L or T+L t reatments. These results indicate that the metabolic actions of leptin are not dependent on a normal thyroid status and that the effects of leptin and T-3 on oxidative metabolism are additive.