Attenuation of diabetes-mediated muscle atrophy in rats by fish oil enriched omega-3 polyunsaturated fatty acids supplementation

Diabetes is associated with an increased risk of muscle wasting/atrophy, which adversely affects quality of life. We hypothesized that long term supplementation of fish oil may have protective effects against sarcopenia or muscle atrophy in streptozotocin (STZ) and high-fat (HF) diet-induced diabetic rat model. Wistar rats at age of 7 weeks were injected with saline or STZ to induce hyperglycemia. After one week, they were fed on a normal control diet or HF diet with/without supplementation of fish oil for 18 weeks. Feeding diabetic rats with a fish oil-enriched diet alleviated body weight loss and the impaired glucose tolerance using OGTT test. Although fish oil did not improve the decreased muscle mass, the muscle atrophy induced by diabetes was attenuated by fish oil in gastrocnemius, soleus, tibialis anterior, and extensor digitorum longus muscles. Fish oil supplementation reversed the decreased expression of phospho (p)-AKT, pmTOR, and p-p70s6k, which are molecules related to protein synthesis. Besides, protein degradation-related signaling pathways were inhibited by fish oil, such as increasing p-FoxO1 and decreasing Atrogin-1 and MURF1 protein expression. Fish oil down-regulated the expression of autophagy-related molecules including ATG5, p62, and LC3B II/I ratio, which may result in less muscle atrophy. Inflammation-related signaling regulators including TNF-α, NF-κB, AGEs, and RAGE were suppressed by fish oil supplementation as well. Moreover, the down-regulated p-AMPKα, SIRT1, and PGC-1 in diabetic rats were counteracted by fish oil, which may improve mitochondrial function and further block FoxO action. These data suggest that long-term fish oil supplementation exerts protective effects against diabetes-induced muscle atrophy, which may in turn ameliorate insulin resistance and impaired glucose tolerance.