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 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 per d) for 4 weeks. Housing in small cages decreased tibialis anterior (TA) muscle mass and the cross-sectional area 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 serine/threonine kinase (Akt), mechanistic target of rapamycin (mTOR) and ribosomal protein S6 kinase (p70S6K) in TA muscle; nevertheless, oleamide increased the phosphorylation levels of the proteins. Housing in small cages increased the expression of microtubule-associated protein 1 light chain 3 (LC3)-II and sequestosome 1 (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 phosphoinositide 3-kinase/Akt/mTOR signalling pathway and restoring autophagy flux.

Autophagy, a catabolic process responsible for the degradation of cytosolic components and the preservation of cellular homeostasis in virtually all eukaryotic organisms, is up-regulated when nutrient supplies are limited. However, whether early weaning induces autophagy in infants is not completely clear. In the present study, we used piglets as the early-weaning model to examine the autophagic activity in different tissues in response to nutrient status. Western blot analysis demonstrated that microtubule-associated protein 1 light chain 3-II, a promising marker protein for macroautophagy, was expressed at a notably higher level at 12 and 24 h weaning treatments than without weaning treatment (P < 0·01), and that the p62 (sequestome 1; SQSTM1) expression level was significantly attenuated after weaning treatments (P < 0·01) in the liver, spleen and skeletal muscle tissues. In addition, autophagic vacuoles detected by transmission electron microscopy were dramatically accumulated in these tissues (P < 0·01). Together, these results indicate that autophagy induced by early weaning may be helpful for the physiological system, which controls the balance of energy and nutrients for basic cell functions in the piglet model.