N-Acetyl-D-valinol

Numerous studies have investigated metabolite alterations resulting from pharmacological treatment in depression models although few quantitative studies explored metabolites exhibiting constant alterations. This study aimed to identify consistently dysregulated metabolites across such studies using a knowledgebase-driven approach. This study was based on 157 studies that identified an assembly of 2757 differential metabolites in the brain, blood, urine, liver, and feces samples of depression models with pharmacological medication. The use of a vote-counting approach to identify consistently upregulated and downregulated metabolites showed that serotonin, dopamine, norepinephrine, gamma-aminobutyric acid, anandamide, tryptophan, hypoxanthine, and 3-methoxytyramine were upregulated in the brain, while quinolinic acid, glutamic acid, 5-hydroxyindoleacetic acid, myo-inositol, lactic acid, and the kynurenine/tryptophan ratio were downregulated. Circulating levels of trimethylamine N-oxide, isoleucine, leucine, tryptophan, creatine, serotonin, valine, betaine, and low-density lipoprotein were elevated. In contrast, levels of alpha-D-glucose, lactic acid, N-acetyl glycoprotein, glutamine, beta-D-glucose, corticosterone, alanine, phenylacetylglycine, glycine, high-density lipoprotein, arachidonic acid, myo-inositol, allantoin, and taurine were decreased. Moreover, 12 metabolites in urine and nine metabolites in the liver were dysregulated after treatment. Pharmacological treatment also increased fecal levels of butyric acid, acetic acid, propionic acid, and isovaleric acid. Collectively, metabolite disturbances induced by depression were reversed by pharmacological treatment. Pharmacological medication reversed the reduction of brain neurotransmitters caused by depression, modulated disturbance of the tryptophan-kynurenine pathway and inflammatory activation, and alleviated abnormalities of amino acid metabolism, energy metabolism, lipid metabolism, and gut microbiota-derived metabolites.

Changes in dietary composition affect the rumen microbiota in ruminants. However, information on the effects of dietary concentrate-to-forage ratio changes on yak rumen bacteria and metabolites is limited. This study characterized the effect of three different dietary concentrate-to-forage ratios (50:50, C50 group; 65:35, C65 group; 80:20, C80 group) on yak rumen fluid microbiota and metabolites using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) analyses. Rumen fermentation parameters and the abundance of rumen bacteria were affected by changes in the dietary concentrate-to-forage ratio, and there was a strong correlation between them. At the genus level, higher relative abundances of norank_f__F082, NK4A214_group, Lachnospiraceae_NK3A20_group, Acetitomaculum, and norank_f__norank_o__Clostridia_UCG-014 were observed with a high dietary concentrate-to-forage ratio (P < 0.05). Combined metabolomic and enrichment analyses showed that changes in the dietary concentrate-to-forage ratio significantly affected rumen metabolites related to amino acid metabolism, protein digestion and absorption, carbohydrate metabolism, lipid metabolism, and purine metabolism. Compared with the C50 group, 3-methylindole, pantothenic acid, D-pantothenic acid, and 20-hydroxy-leukotriene E4 were downregulated in the C65 group, while spermine and ribose 1-phosphate were upregulated. Compared to the C50 group, Xanthurenic acid, tyramine, ascorbic acid, D-glucuronic acid, 6-keto-prostaglandin F1a, lipoxin B4, and deoxyadenosine monophosphate were upregulated in the C80 group, while 3-methylindole and 20-hydroxy-leukotriene E4 were downregulated. All metabolites (Xanthurenic acid, L-Valine, N-Acetyl-L-glutamate 5-semialdehyde, N-Acetyl-L-glutamic acid, Tyramine, 6-Keto-prostaglandin F1a, Lipoxin B4, Xanthosine, Thymine, Deoxyinosine, and Uric acid) were upregulated in the C80 group compared with the C65 group. Correlation analysis of microorganisms and metabolites provided new insights into the function of rumen bacteria, as well as a theoretical basis for formulating more scientifically appropriate feeding strategies for yak.

By far, no study has focused on observing the metabolomic profiles in perimenopause-related obesity. This study attempted to identify the metabolic characteristics of subjects with perimenopause obesity (PO). Thirty-nine perimenopausal Chinese women, 21 with PO and 18 without obesity (PN), were recruited in this study. A conventional ultra-high-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry (UHPLC-QTOF/MS) followed by principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used as untargeted metabolomics approaches to explore the serum metabolic profiles. Kyoto Encyclopedia of Genes and Genomes (KEGG) and MetaboAnalyst were used to identify the related metabolic pathways. A total of 46 differential metabolites, along with seven metabolic pathways relevant to PO were identified, which belonged to lipid, amino acids, carbohydrates, and organic acids. As for amino acids, we found a significant increase in l-arginine and d-ornithine in the positive ion (POS) mode and l-leucine, l-valine, l-tyrosine, and N-acetyl-l-tyrosine in the negative ion (NEG) mode and a significant decrease in l-proline in the POS mode of the PO group. We also found phosphatidylcholine (PC) (16:0/16:0), palmitic acid, and myristic acid, which are associated with the significant upregulation of lipid metabolism. Moreover, the serum indole lactic acid and indoleacetic acid were upregulated in the NEG mode. With respect to the metabolic pathways, the d-arginine and d-ornithine metabolisms and the arginine and proline metabolism pathways in POS mode were the most dominant PO-related pathways. The changes of metabolisms of lipid, amino acids, and indoleacetic acid provided a pathophysiological scenario for Chinese women with PO. We believe that the findings of this study are helpful for clinicians to take measures to prevent the women with PO from developing severe incurable obesity-related complications, such as cardiovascular disease and stroke.