An Omega-3 Fatty Acid-Enriched Diet Prevents Skeletal Muscle Lesions in a Hamster Model of Dystrophy

Abstract

Currently, despite well-known mutational causes, a universal treatment for neuromuscular disorders is still lacking, and current therapeutic efforts are mainly restricted to symptomatic treatments. In the present study, ␦-sarcoglycan-null dystrophic hamsters were fed a diet enriched in flaxseed-derived 3 ␣-linolenic fatty acid from weaning until death. ␣-linolenic fatty acid precluded the dystrophic degeneration of muscle morphology and function. In fact, in dystrophic animals fed flaxseed-derived ␣-linolenic fatty acid, the histological appearance of the muscular tissue was improved, the proliferation of interstitial cells was decreased, and the myogenic differentiation originated new myocytes to repair the injured muscle. In addition, muscle myofibers were larger and cell membrane integrity was preserved, as witnessed by the correct localization of ␣-, ␤-, and ␥-sarcoglycans and ␣-dystroglycan. Furthermore , the cytoplasmic accumulation of both ␤-catenin and caveolin-3 was abolished in dystrophic hamster muscle fed ␣-linolenic fatty acid versus control animals fed standard diet , while ␣-myosin heavy chain was expressed at nearly physiological levels. These findings , obtained by dietary intervention only , introduce a novel concept that provides evidence that the modulation of the plasmalemma lipid profile could represent an efficacious strategy to ameliorate human muscular dystrophy.

Lipid modulation of skeletal muscle mass and function

“…EPA treatment has also been reported to prevent arthritis‐induced reductions in gastrocnemius muscle weight in rats following administration of Freund's adjuvant, concomitant with the normalization of atrogin‐1/MAFbx and MuRF1 gene expression . Moreover, dystrophic hamsters fed a diet enriched in the PUFA α‐linolenic acid (ALA) (C18:3(n‐6)) exhibited improvements in muscle morphology and function, including enlarged myofibres . In accord with these findings, omega‐3 and omega‐6 PUFAs have also been shown to increase phosphorylation of p70S6K1 at Thr389, indicative of its increased activity, during myogenic differentiation of L6 myocytes .…”

“…Notably, these growth suppressing actions have been linked to reduced levels of cyclin E and CDK2, proteins which play a critical role in cell cycle progression, as well as suppressed activation of ERK1/2, a mitogen‐activated protein kinase implicated in promoting cell growth and division . In contrast, feeding dystrophic δ‐sarcoglycan deficient hamsters a diet enriched in ALA (an omega‐3 PUFA) was demonstrated to increase satellite cell proliferation and differentiation in EDL muscle, concomitant with improved muscular histology . Notably, these beneficial responses coincided with the ability of ALA to increase the proportion of α‐MHC positive myofibres in skeletal muscle of dystrophic hamsters, along with a reduction in β‐MHC expression, thereby contributing to the preservation of a more physiological α/β MHC ratio.…”

Alpha-linolenic acid protects against cardiac injury and remodelling induced by beta-adrenergic overstimulation

“…Hence, ALA protective effect was studied in rats using a well-known experimental model of infarct-like myocardial damage obtained by repeated injections of ISO 22,23 . The enrichment of ALA was achieved employing an already validated diet, which was used to address the role of ALA mediated protection in cardiomyocytes and hamsters with genetic cardiomyopaties 18,20,21 . Here, we estimate that 2.85 g/day of ALA was assumed by each rat.…”

“…Firstly, we assessed the triggering of pro-survival pathways in an in vitro model (H9c2 rat cardiomyocytes). Then, we studied the effects of an ALAenriched diet 18,20,21 in adult Wistar rats, which were repeatedly injected with isoproterenol (ISO).…”

Nutritional influences on age-related skeletal muscle loss

“…Recent human studies have found that supplementation with long chain n-3 PUFA increases rates of protein synthesis and augments the muscle protein anabolic response, and may also attenuate acute muscle loss (cachexia) (236)(237)(238)(239)(240)(241) . One small observational study found a negative association with appendicular lean mass and saturated fat, and a comprehensive study of dietary fat composition and muscle mass found positive associations with the PUFA:SFA ratio and negative associations with saturated and trans fatty acids (15,81) .…”