Effects of FADS2 Inhibition in Combination with Increased Dietary n‐3 PUFAs on Skeletal Muscle Protein Turnover in Mice Fed a High Fat Diet.

Polyunsaturated fatty acids (PUFAs) are essential dietary components. They are not only used for energy, but also act as signaling molecules. The delta‐6 desaturase (D6D) enzyme, encoded by the FADS2 gene, is one of two rate limiting enzymes that convert the PUFA precursors – α‐linolenic (n‐3) and linoleic acid (n‐6) to their respective metabolites. Alterations in the D6D enzyme activity alters fatty acid profiles and are associated with metabolic and inflammatory diseases including cardiovascular disease and type 2 diabetes. Omega‐3 PUFAs, specifically its constituent fatty acids DHA and EPA, are known for their anti‐inflammatory capability and may be beneficial in the prevention of skeletal muscle wasting through maintenance of protein turnover. Purpose The purpose of this study was to determine the role of PUFA metabolites in skeletal muscle protein turnover, in the presence or absence of FADS2 activity. Methods Twenty C57BL6 male mice were fed a high‐fat lard (HFL, 45% fat (mostly lard), 35% carbohydrate and 20% protein, n‐6:n‐3 PUFA, 13:1) diet for 6 weeks. Mice were then divided into 2 groups (n=10 per group). One group remained on the HFL diet, while the other group was fed a diet high in n‐3 PUFAs (HFO, 45% fat (mostly Menhaden oil), 35% carbohydrate and 20% protein, n‐6:n‐3 PUFA, 1:3). Each group was further subdivided with half of the animals receiving an orally administered FADS2 inhibitor (100mg/kg/day). After 2 weeks on their respective diets and treatments, animals were sacrificed and gastrocnemius muscle harvested. Protein turnover signaling were analyzed via Western Blot. Results Levels of MTOR and AMPK phosphorylation were measured. There was a trend towards increased MTOR phosphorylation with FADS2 inhibition regardless of diet (p=0.07). There was no difference in phosphorylation of AMPK regardless of diet or inhibitor. We analyzed markers of mitochondrial biogenesis which is closely linked with protein synthesis through PGC1‐α and Cytochrome‐C expression, however no significant differences were associated with either marker across all groups. Conclusion We conclude that by inhibiting the FADS2 enzyme, there is potential for increased protein synthesis via activation of the MTOR pathway. Support or Funding Information University of Memphis School of Health Studies Faculty Research Grant This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .