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

Bowen Li,Guowei Le,Manman Lu,Yuhui Yang,Jing Qian,Yanli Xie

doi:10.3390/foods10102439

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.

Highlights

The widespread prevalence of obesity is a worldwide health problem
Mouse beginning increased compared with that of the significantly decreased the body to the end of the experiment, the body weight of the diet-induced obese (DIO) mice significantly increased compared withcompared that of thewith decreased the body weight weight of mice themice, DIO but miceMR
We found that the activities of respiratory chain enzymes complex I, complex IV, and complex V in spleen were significantly decreased in the DIO mice compared with the CON mice, but the11three of 20 changes were normalized by Methionine restriction (MR) (p < 0.05, Figure 7E)

Summary

Introduction

The widespread prevalence of obesity is a worldwide health problem. Increasing evidence suggests that obesity plays a crucial role in the development of metabolic syndrome, type II diabetes, hypertension, fatty liver diseases, cardiovascular diseases, and some cancers [1,2]. Excessive oxidative stress and chronic inflammation induced by fat accumulation damage cellular structures, leading to multiple organ function damage and the emergence of these obesity-related diseases [3]. As the largest lymphoid organ in the human body, the spleen is currently obtaining more attention for the pivotal role played in modulating inflammation, oxidative stress, immune functions, and fat deposition [4,5]. During obesity, increased levels of oxidative stress and inflammation induced by fat deposition lead to apoptosis of splenic cells and splenic damage, causing immune dysfunction [6]. An increase in oxidative stress and inflammatory response has been demonstrated to be a major mechanism in the pathogenesis and progression of obesity-related spleen diseases [5]. Previous research has suggested that obesity leads to a decrease in the splenic synthesis of anti-inflammatory factors interleukin-10 (IL-10) by promoting oxidative stress [7]

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