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

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 (1H 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.