Abstract: Thyroid hormone plays a very important role in regulating lipid metabolism. This study explored the effect of obesity on thyroid hormone homeostasis in mice and the influence of 1-deoxynojirimycin (DNJ) intervention on this effect. An obese mouse model was established by feeding a high-fat diet, and then DNJ at doses of 8.0, 4.0 and 2.0 mg/(kg mb·d) was administered to the obese mice for 45 days, and serum lipid levels and thyroid hormone related indicators were determined at 5 d intervals during this period. The results showed that compared with the obese control group, high-dose DNJ could significantly alleviate body mass gain and improve dyslipidemia caused by the high-fat diet in female and male mice, as well as increase total thyroxine (TT4) levels by 22.03% and 15.99% (P < 0.05), total triiodothyronine (TT3) levels by 66.86% and 47.79% (P < 0.05), decrease thyroid stimulating hormone (TSH) levels by 9.65% and 9.73% (P < 0.05), increase the activity of liver type 1 deiodinase (DIO1) by 40.99% and 24.40% (P < 0.05) and DIO1 protein levels by 35.68% and 29.50% (P < 0.05), and increase protein levels of liver thyroid hormone receptor β by 37.53% and 27.81% (P < 0.05) in female and male mice, respectively; and it could also significantly up-regulate the mRNA expression of liver DIO1, thyroid hormone receptor β, and the lipid metabolism-related thyroid hormone target genes encoding adipose triglyceride lipase (ATGL), carnitine palmitoyltransferase 1α (CPT1α) and cholesterol 7 alpha-hydroxylase (CYP7A1). In conclusion, DNJ can improve thyroid hormone homeostasis, up-regulate the mRNA expression of the lipid metabolism-related thyroid hormone target genes, and consequently promote lipid catabolism and inhibit body mass gain.

Key words: 1-deoxynojirimycin; thyroid hormone; obesity