Subclinical
hypothyroidism (SCH) is defined as increased serum
thyroid-stimulating hormone (TSH) concentrations and normal serum
thyroid hormone (TH) levels as well as an increased serum
cholesterol level, which is an important cause of secondary
hypercholesterolemia and
cardiovascular diseases. Some studies have demonstrated a direct effect of TSH on
cholesterol metabolism via in vivo and in vitro experiments. However, because no suitable SCH model has been established until now, the changes in
cholesterol synthesis that occur in SCH patients remain unknown. Here, we establish an SCH mouse model by using long-term low-dose MMI administered in
drinking water. Compared with the control group, the MMI-treated mice had elevated circulating TSH levels, but the serum FT3 levels in these mice did not change. Additionally, the TC levels increased in both the serum and liver of the experimental mice. Both the
protein expression and activity of hepatic HMGCR, the rate-limiting
enzyme for
cholesterol synthesis in the liver, increased in these mice. We also found that the SCH mice had decreased phospho-HMGCR and phospho-AMPK expression, while the expression of AMPK showed no change. In conclusion, we established a suitable SCH model in which
cholesterol synthesis is increased.