PMID- 33143796 OWN - NLM STAT- MEDLINE DCOM- 20211214 LR - 20211214 IS - 1475-2662 (Electronic) IS - 0007-1145 (Linking) VI - 126 IP - 4 DP - 2021 Aug 28 TI - Oleamide rescues tibialis anterior muscle atrophy of mice housed in small cages. PG - 481-491 LID - 10.1017/S0007114520004304 [doi] AB - 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. FAU - Kobayashi, Yasuyuki AU - Kobayashi Y AD - Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Osaka5998531, Japan. FAU - Watanabe, Natsumi AU - Watanabe N AD - Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Osaka5998531, Japan. FAU - Kitakaze, Tomoya AU - Kitakaze T AD - Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Osaka5998531, Japan. FAU - Sugimoto, Keiichiro AU - Sugimoto K AD - Research and Development Center, Nagaoka Co. Ltd, Ibaraki, Osaka5670005, Japan. AD - Center for Research and Development of Bioresources, Osaka Prefecture University, Sakai, Osaka5998531, Japan. FAU - Izawa, Takeshi AU - Izawa T AD - Division of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka5988531, Japan. FAU - Kai, Kenji AU - Kai K AD - Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Osaka5998531, Japan. FAU - Harada, Naoki AU - Harada N AUID- ORCID: 0000-0003-3846-388X AD - Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Osaka5998531, Japan. FAU - Yamaji, Ryoichi AU - Yamaji R AUID- ORCID: 0000-0003-4729-3317 AD - Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Osaka5998531, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201104 PL - England TA - Br J Nutr JT - The British journal of nutrition JID - 0372547 RN - 0 (Oleic Acids) RN - 7L25QK8BWO (oleylamide) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Autophagy MH - Housing, Animal MH - Male MH - Mice MH - Muscle Fibers, Skeletal/metabolism MH - Muscle, Skeletal/*drug effects/metabolism MH - *Muscular Atrophy/drug therapy MH - Oleic Acids/*pharmacology MH - *Phosphatidylinositol 3-Kinases/metabolism MH - Phosphorylation MH - Proto-Oncogene Proteins c-akt/metabolism MH - TOR Serine-Threonine Kinases/metabolism OTO - NOTNLM OT - Autophagy OT - Mechanistic target of rapamycin signalling OT - Myotubes OT - Primary fatty acid amides OT - Sedentary behaviour EDAT- 2020/11/05 06:00 MHDA- 2021/12/15 06:00 CRDT- 2020/11/04 05:32 PHST- 2020/11/05 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2020/11/04 05:32 [entrez] AID - S0007114520004304 [pii] AID - 10.1017/S0007114520004304 [doi] PST - ppublish SO - Br J Nutr. 2021 Aug 28;126(4):481-491. doi: 10.1017/S0007114520004304. Epub 2020 Nov 4.