Dietary methionine restriction regulated energy and protein homeostasis by improving thyroid function in high fat diet mice

Abstract

Methionine-restricted diets (MRD) show an integrated series of beneficial health effects, including improving insulin sensitivity, limiting fat deposition, and decreasing oxidative stress, and inflammation responses. We aimed to explore the systemic responses to a MRD in mice fed with a high fat (HFD) and clarify the possible mechanism. Mice were fed with a control diet (0.86% methionine + 4% fat, CON), HFD (0.86% methionine + 20% fat), or MRD (0.17% methionine + 20% fat) for 22 consecutive weeks. HFD-fed mice showed widespread systemic metabolic disorders and thyroid dysfunction. A MRD significantly increased energy expenditure (e.g. fatty acid oxidation, glycolysis, and tricarboxylic acid cycle metabolism), regulated protein homeostasis, improved gut microbiota functions, prevented thyroid dysfunction, increased plasma thyroxine and triiodothyronine levels, decreased plasma thyroid stimulating hormone levels, increased type 2 deiodinase (DIO2) activity, and up-regulated mRNA and protein expression levels of DIO2 and thyroid hormone receptor α1 in the skeletal muscle. These results suggest that a MRD can improve the metabolic disorders induced by a HFD, and especially regulate energy and protein homeostasis likely through improved thyroid function. Thus, reducing methionine intake (e.g. through a vegan diet) may improve metabolic health in animals and humans.

Inulin Can Alleviate Metabolism Disorders in ob/ob Mice by Partially Restoring Leptin-Related Pathways Mediated by Gut Microbiota

“…Arachidonic acid, an unsaturated fatty acid, is positively related to pro-inflammatory cytokines, but inversely correlated with Akkermansia and exacerbates non-alcoholic steatohepatitis (NASH) by promoting the growth of pro-inflammatory bacteria, enhancing the inflammatory response, reducing the abundance of butyrate-producing bacteria, and inducing insulin resistance [34], [35]. A high-fat diet can induce thyroid dysfunction in rodent models, and that the thyroid volume is significantly increased in obese individuals, in contrast to healthy ones [36], [37]. Here, the enrichment scores for Arachidonic acid metabolism and Thyroid hormone synthesis were restored to relatively lower levels after the inulin-supplemented diet.…”

Effects of a high energy and low protein diet on hepatic and plasma characteristics and Cidea and Cidec mRNA expression in liver and adipose tissue of laying hens with fatty liver hemorrhagic syndrome

“…Yang et al. () found that methionine‐restricted diets improved metabolic disorders induced by high fat diet (HFD) in mice. In contrast with this, Jiang et al.…”

Dietary Methionine Restriction Upregulates Endogenous H2S via miR‐328‐3p: A Potential Mechanism to Improve Liver Protein Metabolism Efficiency in a Mouse Model of High‐fat‐diet‐induced Obesity

“…After a 7‐day acclimatization period, C57BL/6J mice were randomly assigned into two groups: the control group fed with the normal diet (CON, n = 30; 0.86% methionine + 4% fat; mainly based on the AIN‐76A formulation, 73%, 17%, and 10% of calories from carbohydrate, protein, and fat, respectively; energy density 3.8 kcal g −1 ; Collaborative Medicine Bioengineering Co., Ltd. Jiangsu, China) or a high‐fat diet group fed with the high fat diet ( n = 90; 0.86% methionine + 24% fat; 41%, 14%, and 45% of calories from carbohydrate, protein, and fat, respectively; energy density 4.7 kcal g −1 ; Collaborative Medicine Bioengineering Co., Ltd. Jiangsu, China) . After 10 weeks of high‐fat diet treatment, given the possibility of the obesity‐resistant mice according to previous reports, 60 heavier mice were numbered and selected as DIO mice.…”

“…Their body weights were significantly higher than those of the control group (41.14 ± 0.62 g vs 30.23 ± 0.41 g, p < 0.01). DIO mice were then divided into two groups: the high fat diet group still fed with the high‐fat diet (HF, n = 30, DIO mice) and the high‐fat + methionine‐restricted diet group fed with the high‐fat and 80%‐methionine‐restricted diet (HF + MR, n = 30, DIO mice; 0.17% methionine + 24% fat; 41%, 14%, and 45% of calories from carbohydrate, protein, and fat, respectively; energy density 4.7 kcal g −1 ; Collaborative Medicine Bioengineering Co., Ltd. Jiangsu, China), respectively . The compositions of three experimental diets are listed (Table S1, Supporting Information).…”