Oleamide rescues tibialis anterior muscle atrophy of mice housed in small cages.

Skeletal muscle atrophy causes decreased physical activity and increased risk of metabolic diseases. We investigated the effects of oleamide (cis-9,10-octadecanamide) treatment on skeletal muscle health. The plasma concentration of endogenous oleamide was approximately 30 nM in the male ddY mice under normal physiological conditions. When the stable isotope-labelled oleamide was orally administered to male ddY mice (50 mg/kg), the plasma concentration of exogenous oleamide reached approximately 170 nM after 1 h. Male ddY mice were housed in small cages (one-sixth of normal size) to enforce sedentary behaviour and orally administered oleamide (50 mg/kg/day) for 4 weeks. Housing in small cages decreased tibialis anterior (TA) muscle mass and the cross-sectional area (CSA) of the myofibres in TA muscle. Dietary oleamide alleviated the decreases in TA muscle and resulted in plasma oleamide concentration of approximately 120 nM in mice housed in small cages. Housing in small cages had no influence on the phosphorylation levels of Akt, mTOR, and p70S6K in TA muscle; nevertheless, oleamide increased the phosphorylation levels of the proteins. Housing in small cages increased the expression of LC3-II and p62, but not LC3-I, in TA muscle, and oleamide reduced LC3-I, LC3-II, and p62 expression levels. In C2C12 myotubes, oleamide increased myotube diameter at ≥ 100 nM. Furthermore, the mTOR inhibitor, Torin 1, suppressed oleamide-induced increases in myotube diameter and protein synthesis. These results indicate that dietary oleamide rescued TA muscle atrophy in mice housed in small cages, possibly by activating the PI3K/Akt/mTOR signalling pathway and restoring autophagy flux.