L-T4 Replacement Therapy On The Expression Of Adipokines And Lipids In SCH Rats

Objectives: This study was designed to establish subclinical hypothyroidism(SCH)model rats by intratracheal administration of methimazole(MMI),aims to observe the effects of different concentrations of thyroid stimulating hormone(TSH)on visceral adipose tissue(VAT)and serum adiponectin(APN),chemerin,tumor necrosis factor-?(TNF-?)and lipilds in subclinical hypothyroidism(SCH)rats,and to clarify the effect of replacement therapy.To determine whether the expressions of APN,chemerin and TNF-? and the changes of lipid have TSH concentration dependence.The changes of the above indexes were also observed after levothyroxine(L-T4)replacement therapy,which provided a certain experimental and theoretical basis for clinical treatment.Methods: Sixty-five male Wistar rats were randomly divided into four groups: control euthyroid group(n = 10),SCH A group(n = 15),SCH B group(n = 15),SCH C group(n = 25)(subgroup A,B,and C groups are collectively referred to as subgroup minus the SCH group).In the SCH rats,form groups A to C were separately induced by administration of 5mg.kg-1.d-1 methimazole(MMI),15 mg.kg-1.d-1 MMI and 20 mg.kg-1.d-1 MMI once daily by gavage.Rat body weight was measured once a week,serum thyroxine and TSH levels were measured once every two weeks.SCH C group rats were successfully established after approximately 8 weeks.Subsequently,10 rats in the SCH C group were randomly divided into L-thyroxine treatment group(SCH+L-T4,n=10),we administered 6 mg/kg/day L-T4 once daily by gavage at the same time as MMI administration until thyroid function was not significantly different from that of control rats.The levels of serum adiponectin,chemerin,TNF-? and serum lipids were measured by Elisa method in 5 groups of rats.The m RNA and protein levels of adiponectin,chemerin and TNF-? in VAT of 5 groups were determined by real-time PCR(RT-PCR)and Western blot.HE staining was used to observe the pathological changes of adipocytes.Results: Compared with the control group,the levels of chemerin and TNF-? in SCH rats were significantly increased and positively correlated with the concentration of TSH(r=0.816,P<0.01;r=0.818,P<0.01),while the level of adiponectin was significantly decreased and negatively correlated with the level of TSH(r=-0.798,P<0.01).L-T4 replacement therapy significantly improved the changes of chemerin,TNF-? and adiponectin(P<0.05).Compared with the control group,serum levels of total cholesterol(TC)and low-density lipoprotein cholesterol(LDL-C)were significantly increased in the SCH group.Compared with the SCH group,L-T4 replacement therapy significantly improved the above-mentioned changes(P <0.05).Conclusion: Elevated TSH levels are closely related to the changes of adipokines and dyslipidemia,but L-T4 treatment can ameliorate these changes.