Hypothyroidism reduces ObRb–STAT3 leptin signalling in the hypothalamus and pituitary of rats associated with resistance to leptin acute anorectic action

Abstract

Leptin has been shown to regulate the hypothalamuspituitary-thyroid axis, acting primarily through the STAT3 pathway triggered through the binding of leptin to the longchain isoform of the leptin receptor, ObRb. We previously demonstrated that although hyperthyroid rats presented leptin effects on TSH secretion, those effects were abolished in hypothyroid rats. We addressed the hypothesis that changes in the STAT3 pathway might explain the lack of TSH response to leptin in hypothyroidism by evaluating the protein content of components of leptin signalling via the STAT3 pathway in the hypothalamus and pituitary of hypothyroid (0 . 03% methimazole in the drinking water/21 days) and hyperthyroid (thyroxine 5 mg/100 g body weight /5 days) rats.Hypothyroid rats exhibited decreased ObRb and phosphorylated STAT3 (pSTAT3) protein in the hypothalamus, and in the pituitary gland they exhibited decreased ObRb, total STAT3, pSTAT3 and SOCS3 (P!0 . 05). Except for a modest decrease in pituitary STAT3, no other alterations were observed in hyperthyroid rats. Moreover, unlike euthyroid rats, the hypothyroid rats did not exhibit a reduction in food ingestion after a single injection of leptin (0 . 5 mg/kg body weight). Therefore, hypothyroidism decreased ObRb-STAT3 signalling in the hypothalamus and pituitary gland, which likely contributes to the loss of leptin action on food intake and TSH secretion, as previously observed in hypothyroid rats.

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“…The fall in leptin level at the same time is being sensed directly by leptin receptors present in TRH neurons; as a consequence of which down regulation of HPT axis occurs. This result is consistent with the findings of Calvino [32], where hypothyroidsm was associated with down regulation of leptin signalling pathway to hypothalamus. We conclude that the dominant and important signal to hypothalamus that suppresses HPT axis and TRH expression is the fall in leptin level which in turn at least partly resulted from reduced adiposity index following FSE feeding in rats.…”

Palmitic acid induces central leptin resistance and impairs hepatic glucose and lipid metabolism in male mice

“…Previously, it has been reported that icv leptin administration increases pSTAT3 immunoreactivity in the PVN neurons of rats [43], and increases pSTAT3 protein in the PVN of mice [44]. However, in the study of Münzberg and colleagues, pSTAT3 immunoreactivity was not altered in the neurons of PVN in mice following the leptin challenge [39].…”

Effects of postnatal bromocriptine injection on thyroid function and prolactinemia of rats at adulthood

“…However, we found, in early-treated BRO animals, a down-regulation of leptin signaling in the ARC, characterized by a reduction in the expression of ObR-b, JAK-2, STAT3 and SOCS3. It has been demonstrated that hypothyroid rats have an inhibited leptin pathway, but with normal leptin serum levels (Calvino et al, 2012).…”