role of leptin in regulation of thyroid hormones secretion and lipid peroxidation in hypothyroid rats

ABSTRACT

We addressed the questions of whether leptin is able to modulate thyroid function. Also, we examined the possible mechanistic interaction between leptin and thyroid hormones. To examine our hypothesis that the effects of leptin on energy metabolism may be regulated independently of the TRH/TSH/thyroid hormones, we have studied the effect of systemic administration of leptin on body weight, some metabolic parameters and levels of thyroid hormones and insulin. Since abnormal thyroid functions may be associated with disturbed lipid metabolism, we also examined the effect of leptin administration on lipid per oxidation during hypothyroid state. Hypothyroidism was induced in adult male Wistar rats by giving them 10 mg methimazole daily with their food for 14 days. The hypothyroid status of the rats was verified by blood hormone levels [3, 3', 5'-triiodo-L-thyroxine [T3], thyroxin [T4], and thyroid stimulating hormone [TSH]]. A total number of 40 hypothyroid rats were randomized into four groups [10 rats each], group I included hypothyroid rats treated with vehicle [V], group II included hypothyroid rats treated by leptin [L], group III included hypothyroid rats treated by T3, group IV included hypothyroid rats treated by both leptin and T3 [L+T3]. An additional group of 10 healthy intact euthyroid rats served as the normal control group [group V]. Initial body weight was measured before the start of leptin and/or T3 treatment and then at the termination of 3 weeks experiment. At the end of the experiments, the serum was used for measurement of cholesterol, triglycerides [TG], free fatty acids [FFA], the levels of leptin, insulin, total T3, T4, TSH, and lipid peroxide. Vehicle treated hypothyroid rats had significant decrease of serum levels of T3, T4, insulin, TG and FFA, and significant increase of TSH and cholesterol levels, while body weight, leptin and lipid peroxide levels were unchanged as compared to controls. Leptin treatment of hypothyroid rats resulted in significant increase of serum leptin levels accompanied by significant increase of FFA and lipid peroxide levels, and significant decrease of body weight, T3, insulin, cholesterol, and TG levels, while, T4 and TSH levels were unchanged as compared to vehicle treated rats. Comparing leptin treated rats with controls, serum T3, T4, TG, insulin levels and body weight were significantly reduced. TSH, leptin, and lipid peroxide levels were significantly increased, while cholesterol and FFA levels were normalized. T3 treatment of hypothyroid rats produced significant decrease of TSH and cholesterol levels and significant increase ofT3, TG, lipid peroxide levels and body weight, and no changes in T4, leptin, FFA, and insulin levels as compared to vehicle treated rats. Comparing T3 treated rats with controls, serum T3, T4, TG, FFA, and insulin levels were significantly reduced, while TSH, cholesterol, lipid peroxide levels and body weight were significantly increased and no change in leptin levels. Combined leptin and T3 treatment caused significant decrease of serum TSH, leptin, cholesterol, TG, FFA, insulin and levels and increase of serum T3, lipid peroxide levels and body weight. No changes in T4 levels were detected as compared to leptin treated rats. By comparing rats treated by both leptin and T3 to controls, there were significant increase of TSH, leptin, lipid peroxide levels and decrease of T4, TG, FFA, insulin levels and body weight and no changes in T3 and cholesterol levels. The current study demonstrates that leptin is capable of reducing body weight, stimulating lipid metabolism and lipid peroxidation in hypothyroid state in rats. It also suggests that the effect of leptin in modulating energy metabolism are not mediated be secondary thyroid messages and are not dependent on a normal thyroid status. The thyroid gland does not constitute an integral component of the leptin action mechanism. However, leptin and thyroid hormones may share some common downstream action sites and can thus act additively, although independently, to enhance calorigenic metabolism, increase lipid peroxidation and attenuate leptin-induced reduction of body weight