Changes in urinary metabolome related to body fat involve intermediates of choline processing by gut microbiota

Abstract

Countering the obesity pandemic will require better understanding of disease mechanisms and development of new diagnostic methods. Small molecule metabolites excreted in urine can be important biomarkers of disease progression and treatment. However, with multiple pathways involved, it has been challenging to identify key pathway(s) that closely follow disease features such as body fat. We employed a high-fat diet (HFD) mouse model of obesity with the goal of determining changes in urinary metabolite profile related to body fat using proton nuclear magnetic resonance ( 1 H NMR). Several urinary metabolites with significantly lower levels in HFD compared to control mice have been identified. Specifically, major changes were found in metabolites from tricarboxylic acid (TCA) cycle, amino acid, nicotinamide, and choline metabolism including 2-hydroxydlutarate, cis -aconitate, trans -aconitate, alanine, creatine, trigonelline, dimethylamine, and trimethylamine. However, levels of only two metabolites, namely dimethylamine and trimethylamine, showed significant reverse correlation with total body fat. These metabolites derive from choline processing by gut microbiota and may be prospective biomarkers indicative of accumulation of body fat in obesity.

Detection of Early Disease Risk Factors Associated with Metabolic Syndrome: A New Era with the NMR Metabolomics Assessment

“…An et al studied the metabolic changes in HFD rats by NMR fecal analysis. HFD rats showed a level reduction of fecal TMA, which its origin is mostly from gut microbiota, probably resulted from its transportation to the liver, where is transformed in TMAO [59]. TMA showed positive correlation with gut microbiota from the genera Allobaculum and Clostridium [60,61].…”

“…To further characterize the metabolic pathways affected by the proposed metabolites, the metabolites were first annotated with Kyoto Encyclopedia of Genes and Genomes (KEGG) [59]. Then, the MetaboAnalyst (v4.0) software was used for metabolic pathway analysis and interpretation [236].…”

The Docosahexanoic Acid: From the Maternal-Fetal Dyad to Early Life Toward Metabolomics

“…Researchers found that lower values of myo-inositol and lactate in urine are related to lower cellular and organism stress, especially for the brain ( 37 ), while N,N-DMG protects the neurodevelopment and the neuronal cell function thanks to its antioxidant function ( 37 ). In an animal study on DMA, a product of choline metabolism by the gut microbiota is reported to be inversely correlated with body fat ( 38 ). The increasing rate of urinary excretion of creatinine, which in previous studies has been positively correlated with weight, height, and postconceptional age, can also be associated with the maturation of infants' renal functions ( 39 ).…”