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Endurance exercise is effective to attenuate muscle atrophy, but the underlying mechanism has not been fully investigated. a\u2010Ketoglutarate (AKG) is a key intermediate of tricarboxylic acid cycle, which is generated during endurance exercise. Here, we demonstrated that AKG effectively attenuated corticosterone\u2010induced protein degradation and rescued the muscle atrophy and dysfunction in a Duchenne muscular dystrophy mouse model. Interestingly, AKG also inhibited the expression of proline hydroxylase 3 (PHD3), one of the important oxidoreductases expressed under hypoxic conditions. Subsequently, we identified the \u00df\n                    <jats:sub>2<\/jats:sub>\n                    adrenergic receptor (ADRB2) as a downstream target for PHD3. We found AKG inhibited PHD3\/ADRB2 interaction and therefore increased the stability of ADRB2. In addition, combining pharmacologic and genetic approaches, we showed that AKG rescues skeletal muscle atrophy and protein degradation through a PHD3\/ADRB2 mediated mechanism. Taken together, these data reveal a mechanism for inhibitory effects of AKG on muscle atrophy and protein degradation. These findings not only provide a molecular basis for the potential use of exercise\u2010generated metabolite AKG in muscle atrophy treatment, but also identify PHD3 as a potential target for the development of therapies for muscle wasting.\u2014Cai, X., Yuan, Y., Liao, Z., Xing, K., Zhu, C., Xu, Y., Yu, L., Wang L., Wang S., Zhu, X., Gao P. Zhang Y. Jiang Q. Xu P. Shu G. \u03b1\u2010Ketoglutarate prevents skeletal muscle protein degradation and muscle atrophy through PHD3\/ADRB2 pathway. FASEB J. 32,488\u2010499 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201700670r","type":"journal-article","created":{"date-parts":[[2017,9,22]],"date-time":"2017-09-22T20:25:27Z","timestamp":1506111927000},"page":"488-499","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["\u03b1\u2010Ketoglutarate prevents skeletal muscle protein degradation and muscle atrophy through PHD3\/ADRB2 pathway"],"prefix":"10.1096","volume":"32","author":[{"given":"Xingcai","family":"Cai","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Animal Nutritional Control College of Animal Science, South China Agricultural University Guangzhou 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