Metabolomics Based on 1H-NMR Reveal the Regulatory Mechanisms of Dietary Methionine Restriction on Splenic Metabolic Dysfunction in Obese Mice

Abstract

Methionine restriction (MR) has been reported to have many beneficial health effects, including stress resistance enhancement and lifespan extension. However, the effects of MR on the splenic metabolic dysfunction induced by obesity in mice remain unknown. This study aimed to investigate the scientific problem and clarify its possible mechanisms. C57BL/6J mice in the control group were fed a control diet (0.86% methionine, 4.2% fat) for 34 weeks, and others were fed a high-fat diet (0.86% methionine, 24% fat) for 10 weeks to establish diet-induced obese (DIO) mouse models. Then, the obtained DIO mice were randomly divided into two groups: the DIO group (DIO diet), the DIO + MR group (0.17% methionine, 24% fat) for 24 weeks. Our results indicated that MR decreased spleen weight, and spleen and plasma lipid profiles, promoted lipid catabolism and fatty acid oxidation, glycolysis and tricarboxylic acid cycle metabolism, and improved mitochondrial function and ATP generation in the spleen. Moreover, MR normalized the splenic redox state and inflammation-related metabolite levels, and increased plasma levels of immunoglobulins. Furthermore, MR increased percent lean mass and splenic crude protein levels, activated the autophagy pathway and elevated nucleotide synthesis to maintain protein synthesis in the spleen. These findings indicate that MR can ameliorate metabolic dysfunction by reducing lipid accumulation, oxidative stress, and inflammation in the spleen, and the mechanism may be the activation of autophagy pathway.

Dietary Methionine Restriction Promotes Fat Browning and Attenuates Hepatic Lipid Accumulation in High-Choline-Fed Mice Associated with the Improvement of Thyroid Function

“…Taken together, these results revealed that MRD significantly attenuated oxidative damage and inflammation in the thyroid of HCD mice. This finding is in agreement with that of our previous study showing that MRD improved oxidative stress and inflammation in the liver, brain, heart, spleen, and intestine of mice. ,,,, Oxidative stress and inflammation can inhibit iodine uptake and impair TH synthesis thus representing major contributors to thyroid dysfunction. , Previous studies showed that improving the oxidative stress and inflammation status can attenuate thyroid dysfunction . Therefore, we believe that MRD protected against thyroid dysfunction in HCD mice through improving redox state and inflammation in the thyroid.…”

“…This finding is in agreement with that of our previous study showing that MRD improved oxidative stress and inflammation in the liver, brain, heart, spleen, and intestine of mice. 41,42,45,54,89 Oxidative stress and inflammation can inhibit iodine uptake and impair TH synthesis thus representing major contributors to thyroid dysfunction. 40,90 Previous studies showed that improving the oxidative stress and inflammation status can attenuate thyroid dysfunction.…”

“…One day after the monitoring period, whole-body composition analysis of the mice (day 88) was conducted as previously described. − MesoMR23-060H-I NMR Analyzer (Shanghai Niumai Electronic Technology Co., Ltd., Shanghai, China) was employed to determine the fat mass and lean mass in mice. NMR Analyzer parameters: magnetic field strength 0.5 ± 0.08 T, resonance frequency 21.3 MHz, and probe coil diameter 60 mm . Percent lean or fat mass (%) = [(lean or fat mass)/body weight] × 100%.…”

Methionine restriction - Association with redox homeostasis and implications on aging and diseases

“…The mechanism by which MR ameliorates oxidative stress during CVD may be the activation of autophagy and hepatic H 2 S generation [ 85 , 124 ]. Activating transcription factor 4 (ATF4) is considered a master regulator of metabolism and is essential for the autophagy gene transcription program [ 125 ].…”

Increased NADPH Supply Enhances Glycolysis Metabolic Flux and L-methionine Production in Corynebacterium glutamicum

“…L-methionine is one of the eight essential amino acids that cannot be synthesized in human and animal bodies and is widely used in food, medicine, feed, and other industries [ 1 , 2 , 3 ]. However, L-methionine is still synthesized by chemical methods at present, and industrial microbial fermentation has not been realized [ 4 ].…”