Effect of levothyroxine replacement therapy on adipocyte expression in subclinical hypothyroidism rats

Abstract

Objective To observe the changes of adiponectin (APN), chemerin and tumor necrosis factor-α (TNF-α) in subclinical hypothyroidism (SCH) rats, and to clarify the effect of L-thyroxine (L-T4) replacement therapy. Methods Sixty-five male Wistar rats were randomly divided into five groups via the random number table method: control group (n= 10), SCH group A (n= 15), SCH group B (n= 15), SCH group C (n= 15) and L-T4 treatment group (SCH + L-T4, n= 10). Rats in groups SCH A, B and C were fed with 5, 15 and 20 mg·kg-1·d-1 methimazole (MMI) once daily by gavage. The rats in SCH + L-T4 group were given 20 mg·kg-1·d-1 MMI once daily through gavage, after 8 weeks, 6 μg·kg-1·d-1 of L-T4 was intragastrically added (50 μg/tablet) and the model was completed at the 16th week. The levels of serum APN, chemerin and TNF-α were measured via the enzyme linked immunosorbent assay (ELISA) method. The mRNA and protein levels of APN, chemerin and TNF-α in visceral adipose tissue of 5 groups were determined by real-time PCR (RT-PCR) and Western blotting, respectively. Results Compared with the control group [(202.20 ± 17.27) ng/L, (143.70 ± 18.46) ng/L, (114.69 ± 4.18) μg/L], the serum chemerin levels in the SCH A, B, C groups were significantly higher [(314.33 ± 16.80), (355.00 ± 17.10), (365.00 ± 11.63) ng/L, P < 0.05] and TNF-α levels also increased significantly [(222.60 ± 14.13), (279.20 ± 12.79), (288.30 ± 15.89) ng/L, P < 0.05], and APN levels were significantly decreased [(77.21 ± 3.08), (68.58 ± 2.92), (59.45 ± 2.41) μg/L, P < 0.05]; but compared with SCH group C, the levels of chemerin and TNF-α in the SCH + L-T4 group were decreased [(260.07 ± 10.80), (178.40 ± 10.29) ng/L] and the level of APN [(102.35 ± 3.17) μg/L] was increased (P < 0.05). The mRNA and protein levels of APN in SCH A, B, C groups were significantly lower than those in the control group (P < 0.05). The APN mRNA and protein levels in the SCH + L-T4 group were significantly higher than those in the SCH group C (P < 0.05). The mRNA and protein levels of chemerin and TNF-α in the SCH A, B, C groups were higher than those in the control group (P < 0.05). However, the mRNA and protein levels of chemerin and TNF-α in the SCH + L-T4 group were significantly lower than those in the SCH group C (P < 0.05). Conclusion The expression levels of serum chemerin and TNF-α in SCH rats have increased, and APN levels decreased, but L-T4 can ameliorate these changes. Key words: Hypothyroidism; Adipokines; L-thyroxine