Global metabolite analyses of serum, muscle and liver reveals a shift in metabolism to favor fatty acid oxidation and energy expenditure (643.10)

Abstract

Global metabolite analysis grouping various pathways represents a powerful and practical means of establishing links to health and disease status. Lipid‐based metabolites, such as the arachidonate (AA)‐derived ligands of the endocannabinoid system (ECS), appear to regulate whole body energy balance and shift anabolic pathways, with overactivation of the ECS associated with obesity and type 2 diabetes. Since ECS activation relies on lipid‐derived ligands, namely AA, we conducted an investigation to determine how dietary PUFA influence the ECS to affect glucose clearance. C57BL/6 mice were fed a control or DHA containing semi‐purified diet for 118 d. Serum, gastrocnemius, and liver were collected after 62 d and 118 d for metabolomics analyses. Epididymal fat mass was lower in mice given DHA but no difference in body weights or food intakes were observed compared to controls. Metabolite profiles portrayed a shift from glucose use to favoring fatty acid oxidation with DHA. Higher levels of DHA‐containing glycerol lipids were found in mice fed the DHA diet, as well as a decrease of AA‐derived ECS ligands, suggesting diminished ECS activation. Analysis of serum oxylipins showed higher levels of LOX and CYP pathway products in mice fed the control diet. These findings demonstrate that mice given DHA suppress the ECS by dampening activation potential resulting in meaningful changes in macronutrient metabolism and physiology.