| Objective: Thyroid hormone played an important role in the energy and lipid metabolism, but the mechanism of it in the development of obesity was still unclear. Studies had shown that micro RNAs played an important role in the regulation of thyroid hormone metabolism. Thus, more attention should be payed to the role of micro RNAs in the development of obesity. Therefore, we established the high-fat diet induced obesity and obesity resistance by feeding high-fat diet. We aimed to investigate whether the high-fat diet could alter the expressions of micro RNAs that can act on the thyroid hormone, and whether this change will influenced the development of obesity and obesity resistance.Methods: Total of 120 C57BL/6 male mice were divided into control group(n=30) and high-fat diet group(n=90). Then, we defined the upper tertiles as the high-fat diet induced obesity group(n=30) and the lower tertiles as the high-fat diet induced obesity resistance group(n=30) in HFD group according to the body weight. 10 mice were selected randomly from every group and sacrificed at 7th week, 17 th week and 27 th week respectively. Energy metabolism of mice were determined by CLAMS, thyroid hormone levels and lipid levels in the plasma were measured. Livers of the three groups were used for micro RNAs sequencing. We determined the m RNA levels of thyroid hormone related micro RNAs, D1, TRβ, and lipid metabolism related genes in the liver. Then, we analyzed the correlation between m RNA levels of hepatic mi R-383, mi R-34 a, mi R-146 b and the contents of plasma TC, TG.Results: When C57BL/6 mice were fed HFD for 7 weeks, mice were designated as diet-induced obesity resistant(DIO-R) and diet-induced obesity(DIO) groups according to the upper and lower tertiles of body weight and kept on feeding until the 17 th week and 27 th week. The body weight of the DIO group was significantly higher than that of DIO-R group and 1.2-fold higher than control(C) group that fed a control diet(P<0.05) in the 7th week, whereas there were no significantly different on body weight between DIO-R group and C group(P<0.05). High-fat diet inhibited the expression of hepatic mi R-383 mi R-34 a and mi R-146 b in DIO and DIO-R group compared to C group. The levels of plasma T4, T3 and protein expression of hepatic D1 in the DIO group were significantly higher than DIO-R group(P<0.05). The m RNA and protein expression of TRβ in DIO-R group both were higher than DIO group in 7th week significantly(P<0.05). The expression of lipogenesis related gene :FAS was higher in DIO group than DIO-R group, the m RNA expression of CPT1α, PGC1α and CYP7A1 were significantly lower in DIO group than DIO-R group in 7th week(P<0.05). The content of TC was significantly higher in the DIO group than DIO-R group in 7th week(P<0.05).In the 17 th week, the expression of hepatic mi R-383, mi R-34 a and mi R-146 b in DIO group were significantly higher than the DIO-R group(P<0.05). Consequently, the protein levels of D1, TRβ and T3 in DIO group were significantly lower than DIO-R group(P<0.05). Meanwhile, the m RNA expression of FAS was higher in DIO group than DIO-R group, the m RNA expression of CPT1α, PGC1α and CYP7A1 were significantly lower in DIO group than DIO-R group(P<0.05). The contents of TC and TG were significantly higher in the DIO group than DIO-R group(P<0.05).In the 27 th week, the m RNA level of mi R-383 in DIO-R group was significant lower than DIO group(P<0.05). The protein expression of hepatic D1 and plasma T3 in the DIO group was significant lower than DIO-R group(P<0.05). Whereas, there were no significant difference of the m RNA expression of mi R-34 a, mi R-146 b, TRβ and protein expression of TRβ among three groups(P>0.05). The m RNA expression of FAS was higher in DIO group than DIO-R group significantly(P<0.05). However, there were no significant difference of the expression of CPT1α, PGC1α and CYP7A1 among three groups(P>0.05). The contents of TC and TG were significantly higher in the DIO group than DIO-R group(P<0.05).Correlation analysis showed that the m RNA level of mi R-383 was significantly negatively related with the protein expression of D1, the m RNA level of mi R-34 a and mi R-146 b were significantly negatively related with the m RNA and protein level of TRβ(P<0.05). The m RNA level of mi R-34 a was significantly positively related to the content of plasma TG and TC. The m RNA level of mi R-146 b was positively related to the content of plasma TG and TC, but not significantly(P>0.05). The m RNA level of mi R-383 showed significantly positively related to the content of plasma TG and positively related to the content of plasma TC.Conclusion: Effects of high-fat diet on the expression of thyroid hormone metabolism related micro RNAs were different. Compared to DIO-R group, the expression of mi R-383 in DIO group was inhibited in the early periods. Whereas, the expression of mi R-34 a and mi R-146 b were evaluated in DIO group, resulting in the expression of TRβ was restrained in later periods. Then, the lipid metabolism regulated by thyroid hormone in DIO group was severer disorded than DIO-R group, and the excess energy was stored in the body as fat. As a consequence, the DIO group showed an higher body weight than DIO-R group. |
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