Calorigenic actions of leptin are additive to, but not dependent on, those of thyroid hormones.
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 (T(3)) replacement (T, 5 microg. 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 T(3) (T). Reduced food consumption and weight gain in the TX rats were reversed by T(3) replacement. Leptin suppressed food intake in the TX rats regardless of T(3) replacement. O(2) consumption (VO(2)) and CO(2) production (VCO(2)) were reduced in TX rats (P < 0.05 vs. normal) but were normalized by either T(3) or leptin treatment. T+L additively increased VO(2) and VCO(2) (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 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 T(3) on oxidative metabolism are additive.
Wang
J L
JL
Departments of Pharmacology and Pathology, Amgen Center, Thousand Oaks, California 91320-1789, USA.
Chinookoswong
N
N
Yin
S
S
Shi
Z Q
ZQ
D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002153:Calorimetry, Indirect; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D007037:Hypothyroidism / Q000188:drug therapy / Q000378:metabolism*; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013965:Thyroidectomy; D014284:Triiodothyronine / Q000494:pharmacology*
D020738:Leptin; D014284:Triiodothyronine