Dietary Docosahexaenoic Acid and Glucose Systemic Metabolic Changes in the Mouse
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 conducted to determine wh...
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| Format: | Article |
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MDPI AG
2023-06-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/15/12/2679 |
| _version_ | 1797593183530516480 |
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| author | Bruce A. Watkins John W. Newman George A. Kuchel Oliver Fiehn Jeffrey Kim |
| author_facet | Bruce A. Watkins John W. Newman George A. Kuchel Oliver Fiehn Jeffrey Kim |
| author_sort | Bruce A. Watkins |
| collection | DOAJ |
| description | 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 conducted to determine whether dietary PUFA could influence the ECS to affect glucose clearance by measuring metabolites of macronutrient metabolism. 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 promotion of fatty acids as substrate were found based on levels of metabolic pathway intermediates and altered metabolic changes related to pathway 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. |
| first_indexed | 2024-03-11T02:05:20Z |
| format | Article |
| id | doaj.art-6ee6514b1dc64f63ae36bdea68aef636 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-11T02:05:20Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-6ee6514b1dc64f63ae36bdea68aef6362023-11-18T11:56:05ZengMDPI AGNutrients2072-66432023-06-011512267910.3390/nu15122679Dietary Docosahexaenoic Acid and Glucose Systemic Metabolic Changes in the MouseBruce A. Watkins0John W. Newman1George A. Kuchel2Oliver Fiehn3Jeffrey Kim4Department of Nutrition, University of California, Davis, Davis, CA 95616, USAUnited States Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, Davis, CA 95616, USACenter on Aging, University of Connecticut Health Center, Farmington, CT 06030, USANIH UC Davis West Coast Metabolomics Center, Davis, CA 95616, USAGenome and Biomedical Sciences Facility, University of California, Davis, Davis, CA 95616, USAThe 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 conducted to determine whether dietary PUFA could influence the ECS to affect glucose clearance by measuring metabolites of macronutrient metabolism. 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 promotion of fatty acids as substrate were found based on levels of metabolic pathway intermediates and altered metabolic changes related to pathway 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.https://www.mdpi.com/2072-6643/15/12/2679DHAmetabolomicsendocannabinoidsC57/blk6 miceplasmamuscle |
| spellingShingle | Bruce A. Watkins John W. Newman George A. Kuchel Oliver Fiehn Jeffrey Kim Dietary Docosahexaenoic Acid and Glucose Systemic Metabolic Changes in the Mouse Nutrients DHA metabolomics endocannabinoids C57/blk6 mice plasma muscle |
| title | Dietary Docosahexaenoic Acid and Glucose Systemic Metabolic Changes in the Mouse |
| title_full | Dietary Docosahexaenoic Acid and Glucose Systemic Metabolic Changes in the Mouse |
| title_fullStr | Dietary Docosahexaenoic Acid and Glucose Systemic Metabolic Changes in the Mouse |
| title_full_unstemmed | Dietary Docosahexaenoic Acid and Glucose Systemic Metabolic Changes in the Mouse |
| title_short | Dietary Docosahexaenoic Acid and Glucose Systemic Metabolic Changes in the Mouse |
| title_sort | dietary docosahexaenoic acid and glucose systemic metabolic changes in the mouse |
| topic | DHA metabolomics endocannabinoids C57/blk6 mice plasma muscle |
| url | https://www.mdpi.com/2072-6643/15/12/2679 |
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