Adipose-specific inactivation of thyroid stimulating hormone receptors in mice modifies body weight, temperature and gene expression in adipocytes

Background: In obesity, the expression level of thyroid stimulating hormone receptor in adipose tissue is reduced and the levels of thyroid stimulating hormone (TSH) are often elevated within the normal range.

Purpose/aim: To investigate the role of TSHR in brown and white adipose tissue (AT) using TSHR knockout (KO) mice and the physiological phenotypes affected by the TSHR knockout.

Methods: AT-specific TSHR KO male mice and wild type (WT) controls were given a high-fat diet (HFD) or a control diet (CD). Body weights and food consumption were recorded for 20 weeks and body temperatures for the first 3 weeks. At termination, white and brown adipocytes were isolated. Gene expressios was investigated using real-time PCR. In a subgroup of female KO mice, glucose tolerance was investigated.

Results: TSHR were partially knocked out in KO mice, which gained more weight than WT mice when fed both a CD (p = .03) and HFD (p = .003). Body temperatures were lower in KO mice on CD (p <.001) and on HFD (p <.001) than WT controls. This was in agreement with reduced gene expression of UCP1 in brown adipocytes in the KO mice. Glucose tolerance was significantly impaired in KO mice on CD mice before termination (p <.01). Expression of adipogenic and lipolytic genes were reduced in KO mice, which was exacerbated by HFD. The mRNA levels of adipokines including ADIPOQ and LEP were altered in white adipocytes of KO mice.

Conclusions: TSHR KO led to dysfunction of both white and brown AT and predisposition to excess body weight gain in mice. Our data show that TSHR in AT regulates glucose tolerance, lipid metabolism, adipokine profile, and thermogenesis.