Thesis Defense Announcement

School of Health Studies announces the Final Thesis Defense of

Katie Brown

for the Degree of Master of Science

March 29, 2019 at 9:00 AM in Fieldhouse, Room 166 

Advisor: Melissa Puppa

Effect of omega-3 supplementation in high-fat diet on skeletal muscle protein degradation in glucocorticoid-induced muscle wasting

ABSTRACT: Background: Muscle atrophy underlies many diseases. Glucocorticoids are used as a therapeutic treatment against inflammation, yet elicit harmful effects to muscle mass. Much of the western population consumes a high-fat diet high in n-6/n-3, which is known to exacerbate detrimental effects of glucocorticoids. Altering the n-6/n-3 ratio has been of interest as omega-3s have proven beneficial in muscle protein turnover. Evidence of omega-3 supplementation with glucocorticoids, however, is variable. Further, the effects of n-3 supplementation in a high fat diet on glucocorticoid-induced muscle atrophy is unknown. Methods: Male wild type C57BL/6 mice were randomized into two groups (n=32): 45% lard/Western diet (HFL, 45% fat (177.5 g lard), 35% carbohydrate, and 20% protein, n-6:n-3 PUFA, 13:1), and 45% omega-3 rich diet (n-3, 45% fat (177.5 g Menhaden oil), 35% carbohydrate, and 20% protein, n-6:n-3 PUFA, 1:3). After 4 weeks on their respective diets, both groups were each divided in half to receive either daily subcutaneous injections of dexamethasone (3 mg/kg/day) or sterile PBS while consuming their diets for the remaining week. Results: Dexamethasone significantly reduced white gastrocnemius weight by 12% independently of diet composition. Protein degradation signaling was altered by dexamethasone with increased atrogin-1 expression; there was an effect of dexamethasone to decrease phosphorylation of FOXO3a, increase phosphorylation of GSK-3b, and increase myostatin and MURF-1 gene expression. However, the negative effects of dexamethasone were not attenuated by omega-3 supplementation. Conclusion: These data support the deleterious effects of dexamethasone on muscle atrophy via upregulation of the UPS, regardless of an omega-3 high-fat diet.