Hind limb suspension and long-chain omega-3 PUFA increase mRNA endocannabinoid system levels in skeletal muscle

Muscle disuse has numerous physiological consequences that end up with significant catabolic metabolism and ultimately tissue atrophy. What is not known is how muscle atrophy affects the endocannabinoid (EC) system. Arachidonic acid (AA) is the substrate for anandamide (AEA) and 2-arachidonylgycerol (2-AG), which act as agonists for cannabinoid receptors CB1 and CB2 found in muscle. Diets with n-3 polyunsaturated fatty acids (PUFA) have been shown to reduce tissue levels of AA, AEA and 2-AG. Therefore, we hypothesized that hind limb suspension (HS)-induced muscle atrophy and intake of n-3 PUFA will change mRNA levels of the EC system. Mice were randomized and assigned to a moderate n-3 PUFA 11.7 g/kg eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA)], high n-3 PUFA (17.6 g/kg EPA+DHA) or control diets for 12 days and then subjected to HS or continued weight bearing (WB) for 14 days. HS resulted in body weight, epididymal fat pad and quadriceps muscle loss compared to WB. Compared to WB, HS had greater mRNA levels of AEA and 2-AG synthesis enzymes and CB2 in the atrophied quadriceps muscle. The high n-3 PUFA diet resulted in greater mRNA levels of EC synthesis enzymes, and CB1 and CB2. The higher mRNA levels for EC with HS and dietary n-3 PUFA suggest that muscle disuse and diet induce changes in the EC system to sensitize muscle in response to metabolic and physiological consequences of atrophy.