Supplementation with dietary EPA/DHA influences red blood cell fatty acid desaturase estimates and reflects tissue changes in fatty acids in systemic organs

Abstract

Delta‐5‐desaturase (D5D) and delta‐6‐desaturase (D6D) are critical in polyunsaturated fatty acid (PUFA) metabolism. D5D and D6D catalyze the conversion of linoleic acid (LA) into arachidonic acid (AA) and that of alpha‐linolenic acid (ALA) into eicosapentaenoic acid (EPA). Altered PUFA desaturation (i.e., increased D6D and decreased D5D) can exacerbate inflammatory responses. Supplementation with the long chain PUFAs (LCPUFAs) EPA and DHA can influence PUFA metabolism and decrease pro‐inflammatory responses. Furthermore, changes in D5D and D6D activity are associated with obesity, type‐2 diabetes, and dysregulated metabolism. The objective of this study was to determine how increasing dietary EPA and DHA alters the D5D and D6D enzyme activity estimates (EAEs) in the RBC (red blood cell) and systemic tissues. In this study, mice were fed control plus three diets with increasing percent of energy (%en) derived from EPA+DHA. Dietary levels reflected recommended intakes of fish/fish oil by the American Heart Association. These doses translated to 0.1%en, 0.675%en, and 1.8%en from dietary EPA+DHA. Phospholipid (PL) fatty acids (FAs) were isolated from heart, skeletal muscle, spleen, lung, adipose tissue, and RBCs. PL FAs were converted to FA methyl esters and analyzed using gas chromatography. D5D and D6D EAEs were calculated using the ratio of arachidonic/dihomo‐gamma linolenic acid (DGLA) and DGLA/linoleic acid, respectively. We observed a positive correlation between RBC D5D EAEs and tissue D5D EAEs across all tissues. RBC D6D EAEs were positively correlated with muscle and negatively correlated with adipose D6D EAEs. D5D and D6D EAEs varied with EPA+DHA supplementation. When comparing the control vs the 1.8%en EPA+DHA diets, a significant decrease in D5D EAE was observed in heart (−42.51%), lung (−54.99%), spleen (−51.46%), and adipose (−78.06%). No significant difference was observed in muscle D5D EAE. Muscle D6D EAE significantly decreased (−39.95%). In adipose tissue, D6D was significantly increased compared to control (+97.80%). No significant dietary effect on D6D EAE was observed in heart, lung, or spleen with supplementation. RBC desaturase EAEs are reflective of tissue desaturase EAEs. Interestingly, RBC desaturase EAEs remained reflective of tissue desaturase EAEs despite changes in mean D5D and D6D EAEs after EPA+DHA supplementation. The high correlation between RBC desaturase EAEs and tissue desaturase EAEs with increasing dietary EPA and DHA, indicates RBC D5D and D6D EAEs are accurate non‐invasive methods to assess tissue PUFA metabolism. Future studies should investigate the usefulness of RBC desaturases in assessing tissues desaturases in disease models such as obesity, type‐2 diabetes, and metabolic syndrome and how EPA+DHA may alter fatty acid metabolism to favor an anti‐inflammatory profile.Support or Funding InformationResearch Support: NIH R03CA142000