Dietary docosahexaenoic acid and glucose systemic metabolic changes in the mouse

Authors: WATKINS, BRUCE - University Of California, Davis; Newman, John; KUCHEL, GEORGE - University Of Connecticut; FIEHN, OLIVER - University Of California, Davis; KIM, JEFFREY - University Of California, Davis

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/6/2023
Publication Date: 6/8/2023
Citation: Watkins, B., Newman, J.W., Kuchel, G.A., Fiehn, O., Kim, J. 2023. Dietary docosahexaenoic acid and glucose systemic metabolic changes in the mouse. Nutrients. 15(12). Article 2679. https://doi.org/10.3390/nu15122679.
DOI: https://doi.org/10.3390/nu15122679

Interpretive Summary: The endocannabinoid system (ECS) participates in regulating whole body energy balance and can be overactive and negatively associated with obesity and type 2 diabetes. Activators of the ECS include metabolites of fats and a study was conducted to determine if dietary fats could influence the ECS to influence glucose clearance. Mice were fed a control or docosahexaenoic acid (DHA)-enriched semi-purified diet for a period of 112 d. Plasma and tissues were collected and analyzed for metabolomics in the middle and at the end of this feeding. The DHA feeding increased the use of fats for energy, increased level of DHA in glycerolipids, and may restore ECS tone by lowering arachidonic acid derived endocannabinoids.

Technical Abstract: The endocannabinoid system (ECS) participates in regulating whole body energy balance. Overactivation of the ECS has been associated with the negative consequence of obesity and type 2 diabetes. Since activators of the ECS rely on lipid-derived ligands an investigation was carried out to determine whether dietary PUFA could influence the ECS to affect glucose clearance. C57/blk6 mice were fed a control or DHA-enriched semi-purified diet for a period of 112 d. Plasma, skeletal muscle, and liver were collected after 56 d and 112 d of feeding the diets for metabolomics analysis. Key findings characterized a shift in glucose metabolism and greater catabolism of fatty acids in mice fed the DHA diet. Glucose use and promoting fatty acids as substrate was found based on levels of metabolic pathway intermediates and altered metabolic flux with DHA feeding. Greater levels of DHA-derived glycerol lipids were found subsequently leading to the decrease of arachidonate derived endocannabinoids (eCB). Levels of 1- and 2-arachidonylglcerol eCB in muscle and liver were lower in the DHA-diet group compared to controls. These findings demonstrate that DHA feeding in mice alters macronutrient metabolism and may restore ECS tone by lowering arachidonic acid derived eCB.