Effects of omega‑3‑ and omega‑6‑rich high‑fat diets on skeletal muscle protein degradation signaling in glucocorticoid‑treated mice

Omega‑3 polyunsaturated fatty acids elicit beneficial effects in several muscle atrophy conditions; however, little is known about the effects of changing the ratio of omega‑3s in high‑fat diet feeding coupled with glucocorticoid treatment. The present study sought to determine whether a high‑fat diet rich in n‑3 is protective of glucocorticoid‑induced protein degradation. For this purpose, male wild‑type C57BL/6 mice were randomly divided into two groups as follows: n‑6 (45% fat, 177.5 g lard) and n‑3 (45% fat, 177.5 g Menhaden oil). Following a period of 4 weeks on their diets, the mice in the groups were divided to receive either daily injections of dexamethasone (Dex; 3 mg/kg/day) or sterile PBS, for 1 week while continuing the diets. Dex reduced gastrocnemius weight by 12% independently of diet. Protein degradation signaling was altered by Dex with an increased expression of atrogin‑1, the decreased phosphorylation of forkhead box O3, the increased phosphorylation of glycogen synthase kinase‑3β, and the increased expression of myostatin and the muscle RING‑finger protein‑1 gene in red, but not white gastrocnemius muscle. However, the negative effects of Dex were not prevented by an n‑3 high‑fat diet. On the whole, these data support the detrimental effects of Dex on muscle atrophy and report mild benefits of an n‑3 high‑fat diet.