Background
Thyroid-stimulating hormone (TSH) is an independent risk factor of and closely associated with metabolic disorders. In the present study, we explored the potential mechanism and adverse effects of TSH on insulin resistance in the liver of subclinical hypothyroidism models in vivo.
Conclusion
TSH may participate in aggravating inflammation by increasing macrophage infiltration; furthermore, it may activate the TLR4-associated inflammatory signaling pathway, thus interfering with insulin signals in liver tissues. Targeting TSH may have therapeutic benefits against metabolic disorders.
Methods
The mean glucose infusion rate (GIR), free fatty acids (FFAs), the homeostatic model assessment for insulin resistance (HOMA-IR), fasting plasma insulin (FINS), the TLR4 signal pathway and its intracellular negative regulator-toll-interacting protein (Tollip), and the modulators of insulin signaling were evaluated.
Results
Compared to the normal control group (NC group), the subclinical hypothyroidism rat group (SCH group) showed decreases in GIR and increases in FFAs, FINS, and HOMA-IR. The levels of TLR4 and of its downstream molecules like p-NF-κB, p-IRAK-1, IL-6 and TNF-α were evidently higher in the SCH group than in the NC group. Conversely, the level of Tollip was significantly lower in the SCH group than in the NC group. Compared to the NC group, the levels of phosphorylated IRS-1-Tyr and GLUT2 were decreased in the SCH group. Macrophage infiltration was higher in the SCH group than in the NC group.