Higher hepatic sterol-binding protein-2 gene expression and serum triglyceride level in methimazole induced subclinical hypothyroid animal model

Subclinical hypothyroidism (SCH) is a thyroid disorder characterized with elevated TSH level. Recent investigations indicate association of SCH with cardiovascular complications and dyslipidemia. Here, we aimed to evaluate the dyslipidemia in rat model of SCH induced with methimazole (MM) administration. For SCH induction, MM was administrated using gavage or ad libitum in drinking water to rats. Serum TSH and T4 levels were measured using ELISA method. The cholesterol and triglyceride were measured in serum samples using colorimetric assays. Lipid accumulation in the liver tissue was assessed histologically using oil red-o staining method. Gene expression alteration of the lipid hemostasis associated genes including acetyl CoA carboxylase (ACC), fatty acid synthase (FASN), and sterol-binding protein 2 (SREBP-2) were measured using qRT-PCR method in hepatocyte of treated animals. Our findings showed that MM can successfully induce SCH in rats by gavage; however, MM administration in drinking water was not efficient. The serum samples from SCH rat showed higher triglyceride (P value = 0.005) and total cholesterol (P value > 0.05) level. The accumulation of lipid droplets found in larger size (P value < 0.0001) in hepatocyte of the SCH rat comparing to the control. The gene expression of ACC, FASN, and SREBP-2 (~1.5 fold change) was upregulated in SCH rats; however, the changes of SREBP-2 expression were significant (P value = 0.04). It can be concluded that MM delivery through drinking water is not efficient enough for SCH modeling when comparing to gavage delivery. Altogether, we found MM-gavage-induced SCH rats have higher triglyceride level in circulation with increased lipid droplets size and elevated SREBP-2 transcription factor gene expression in hepatocytes.