Congenital Hypothyroidism is Associated With Impairment of the Leptin Signaling Pathway in the Hypothalamus in Male Wistar Animals in Adult Life

Abstract

The goal of this study is to investigate whether congenital hypothyroidism induced by MMI during gestation (G) or gestation plus lactation (GL) would affect the leptin action upon body weight control on hypothalamus. Six to eight pups per group were killed at 90 days of age. For statistical analysis one-way ANOVA followed by the Holm–Sìdak post hoc test was used. Hypothyroidism resulted in a significant increase in leptin serum levels in G 20% and GL 25% (p<0.04). There was a significant expression decrease of OBR in G 45% and GL 63%; pSTAT3 in G 56% and GL 51%; pERK in G 50% and GL 48%; POMC in G 41% and GL 46% (p<0.04), while a significant increase was assigned to SOCS3 in G 52% and GL 170% (p<0.04) protein expression. We can conclude that hypothyroxinemia condition in rats on adulthood results in impairment of the leptin signaling pathway via ObRb-STAT3 in the hypothalamus, which is likely to be involved in the leptin resistance.

Thyroid Deficiency Before Birth Alters the Adipose Transcriptome to Promote Overgrowth of White Adipose Tissue and Impair Thermogenic Capacity

“…Further investigations are required, however, to determine whether these programming effects arise directly from the altered adipose phenotype and/or indirectly from other changes in endocrine activity, metabolism, or appetite regulation that affect adult adiposity. For example, antithyroid drug treatment in pregnant rats leads to hyperleptinemia in the adult offspring and alterations in hypothalamic leptin signaling molecules indicative of leptin resistance (59). Hyperinsulinemia and overgrowth of UL adipose tissue in sheep fetuses infused with glucose were also associated with changes to the expression of neuropeptides in the appetite-regulatory regions of the hypothalamus (37).…”

The joint effect of congenital hypothyroidism and hypercaloric diet consumption as triggers of type 2 diabetes mellitus

“…Thyroid hormone (T 3 ) is one of the responsible hormones for bodyweight regulation because it modulates long-term bodyweight programs related to the leptin and insulin pathways ( 15 , 24 , 25 ). Rats fed a hypercaloric diet for 40 weeks had the highest hyperleptinemia levels with physiological leptin resistance.…”

“…Rats fed a hypercaloric diet for 40 weeks had the highest hyperleptinemia levels with physiological leptin resistance. But usually, the leptin resistance can only be demonstrated by a molecular evaluation of hypothalamic SOCS3 overexpression because energy intake does not change ( 14 , 15 ). The results obtained show that a mild disturbance in the lipid contents of the diet produces metabolic damage, causing dyslipidemia, hyperleptinemia, and alterations in cardiovascular risk markers as Castelli index I and II.…”

“…On the other hand, previously in animal models, we reported the increased risk to develop T2D in congenital hypothyroid rats because they develop metabolic syndrome even when they are fed with a standard-balanced diet ( 12 , 13 , 14 ). The mentioned studies reveal that congenital hypothyroidism modifies the metabolic programming promoting dyslipidemia and hyperleptinemia with a change in the thyroid gland’s function ( 12 , 15 ). These conditions could be seen severely increased when a hypercaloric diet is administered because it induces epigenetic methylation patterns in adipocyte-associated metabolic dysfunction ( 16 ).…”