The effects of Methionine restriction on thyroid hormones and mitochondrial changes in skeletal muscle

Abstract

Dietary methionine restriction (MR) limits fat deposition and reduces adiposity without food restriction, despite increasing total food intake. Recent reports have shown that MR have an effect on generating thyroid hormones, which are associated with mitochondrial biogenesis. However, the effect of thyroid hormones on skeletal muscle mitochondria content and function is unknown when MR in a high‐fat diet (HFD). This study investigated the potential mechanisms of THs on mitochondrial content and function in mice skeletal muscle induced by MR administration with HFD. C57Bl/6 male mice were randomly divided into three groups: a low‐fat diet (LFD) group, a HFD group and a MR‐HFD group. In the 12th week, half of the mice were sacrificed and the remaining mice were kept on feeding and sacrificed in the 23th week. Indices about THs, mitochondria, oxidative stress, relative gene expression and protein expression in mice skeletal muscle were assayed. In the 12th week, HFD mice showed a significant body weight gain, high circulating THs levels and activated HPT axis, whereas MR‐HFD mice had normal body weight although with high THs levels and activated HPT axis. In the 23th week, HFD mice had low THs levels, whereas MR‐HFD mice maintained TH levels. Genes involved in THs production were downregulated in HFD and up‐regulated in MR‐HFD mice. An increase in mitochondrial membrane potential, ATP generation, mitochondrial DNA copy number was observed in skeletal muscle MR‐HFD mice, all these were downregulated in HFD mice, however. Furthermore, MR‐HFD enhanced gene expression involved in mitochondrial function and protein expression of mitochondrial complex□. The results indicate that persistent increased THs in methionine‐restricted mice is associated with boosted mitochondrial content and function in skeletal muscle.Support or Funding InformationThis research was supported by program of “Collaborative innovation center of food safety and quality control in Jiangsu Province”, the National Natural Science Foundation of China (No. 31571841), State Key Laboratory of Food Science and Technology of Jiangnan University in China (SKLF‐ZZB‐201609).