Modulatory Role of NTSR1 Antagonist SR48692 in HFD-Induced Thyroid Impairment in Mice: An <i>In Vivo</i> Study

Abstract

Thyroid hormones are one of the crucial regulators of metabolism, especially lipid, and is linked with lipid metabolism dysregulation. High-Fat Diet (HFD) induces the secretion of Neurotensin (NTS), which enhances lipid absorption, and deposition, proportionately increases leptin. Increased leptin is associated with central leptin resistance and affects thyroid regulation which may lead to hypothyroidism. We hypothesized that HFD-induced increased NTS may cause dyslipidemia leading to thyroid alterations, which could be antagonized by the NTS receptor-1 (NTSR1) antagonist SR48692. Swiss albino mice (n = 24) were divided into two sets and fed with Standard Diet (SD) and HFD for 4 weeks. After that each set of mice were further divided into two groups and administered with 0.9% saline and SR48692 (100 μg/kg bw) intraperitoneally for 4 weeks and maintained as Group-I: (Control/SD), Group-II: (HFD), Group-IV: (HFD+SR48692), and Group-IV: (SD+SR48692). HFD-fed mice showed significantly decreased T3 and T4 with increased TSH and leptin, suggesting leptin-induced hypothyroidism, also reflected in the histological alterations observed in thyroid and adipose tissue. Co-treatment with SR48692 (HFD+SR48692) showed amelioration in the thyroid, as levels of T3, T4, TSH, and resensitization of leptin, were evident in histopathological analysis compared to HFD suggesting the therapeutic efficacy of SR48692 on thyroid impairment in dyslipidemia. Only SR48692-treated group showed an exacerbating effect.