Metabolomic Analysis of Livers and Serum from High-Fat Diet Induced Obese Mice

Abstract

Liver and serum metabolites of obese and lean mice fed on high fat or normal diets were analyzed using ultraperformance liquid chromatography-quadrupole-time-of-flight mass spectrometry, gas chromatography-mass spectrometry, and partial least-squares-discriminant analysis (PLS-DA). Obese and lean groups were clearly discriminated from each other on PLS-DA score plot and major metabolites contributing to the discrimination were assigned as lipid metabolites (fatty acids, phosphatidylcholines (PCs), and lysophosphatidylcholines (lysoPCs)), lipid metabolism intermediates (betaine, carnitine, and acylcarnitines), amino acids, acidic compounds, monosaccharides, and serotonin. A high-fat diet increased lipid metabolites but decreased lipid metabolism intermediates and the NAD/NADH ratio, indicating that abnormal lipid and energy metabolism induced by a high-fat diet resulted in fat accumulation via decreased β-oxidation. In addition, this study revealed that the levels of many metabolites, including serotonin, betaine, pipecolic acid, and uric acid, were positively or negatively related to obesity-associated diseases. On the basis of these metabolites, we proposed a metabolic pathway related to high-fat diet-induced obesity. These metabolites can be used to better understand obesity and related diseases induced by a hyperlipidic diet. Furthermore, the level changes of these metabolites can be used to assess the risk of obesity and the therapeutic effect of obesity management.

Distinct signatures of host–microbial meta-metabolome and gut microbiome in two C57BL/6 strains under high-fat diet

“…Many of these studies investigated the particular role of metabolites in inflammatory bowel diseases by using primarily NMR studies (Lin et al, 2011). Non-targeted metabolomics approaches in gut microbial sample matrices and liver, analysing changes occurring in metabolic diseases like obesity, are rarely given, but many studies addressed obesity-related metabolome characterization (Dumas et al, 2006;Williams et al, 2006;Fearnside et al, 2008;Li et al, 2008Li et al, , 2010aShearer et al, 2008;Newgard et al, 2009;Waldram et al, 2009;Kim et al, 2009Kim et al, , 2010Kim et al, , 2011Calvani et al, 2010;Xie et al, 2010Xie et al, , 2012Zhao et al, 2010;Oberbach et al, 2011;Duggan et al, 2011a,b;Jung et al, 2012;Hanhineva et al, 2013;Schäfer et al, 2014;Seyfried et al, 2013;Won et al, 2013;Xu et al, 2013;Daniel et al, 2014;Eisinger et al, 2014). Comparing with other studies, our study provides a greater insight into different metabolite classes that were involved in obesity-related changes by reflecting both bacterial and host metabolism.…”

NAD + and SIRT3 control microtubule dynamics and reduce susceptibility to antimicrotubule agents

“…Based on our finding that NAD + can prevent vinblastineinduced microtubule depolymerization, it is conceivable that physiological or disease states associated with increased or decreased NAD levels will be more resistant or more responsive, respectively, to the effects of vinblastine and related antimicrotubule agents. For example, aging and obesity are associated with decreased biosynthesis of NAD + (60)(61)(62)(63). In contrast, calorie restriction is associated with increased NAD + (64).…”

Metabolomics in diabetes research

“…Moreover, regarding purine metabolism and the Krebs cycle, a complex metabolic perturbation in HFRD rats was observed. Increased levels of phospholipids and fatty acid were also found in high-fat-fed mice in combination with lower levels of betaine, carnitine and acylcarnitines, which are metabolites involved in lipid metabolism (Kim et al 2011). In liver and skeletal muscle tissue, a high-fructose diet leads to oxidative stress, elevated levels of amino acids and alterations in fatty acid biosynthesis, whereas this type of diet is related to decreased amino acid levels and the up-regulation of purine biosynthesis in the cerebral cortex and hippocampus (Lin et al 2011).…”