Acute exercise can alter the abundance of key metabolic proteins in skeletal muscle. These effects are influenced by postexercise (PEX) refeeding. Muscle glycogen resynthesis is a putative mediator of these refeeding effects. However, it is challenging to test this idea, because glycogen resynthesis is only one of many outcomes with refeeding. Therefore, we devised a novel genetic model to modify muscle expression of glycogen synthase 1 (GS1) using injection of rat skeletal muscle with adeno-associated viral (AAV) vectors for short hairpin RNA targeting GS1 (shRNA-GS1). Contralateral muscles were injected with scrambled shRNA (shRNA-Scr). Rats were sedentary (SED) or exercised (120min swim-exercise). Muscles were collected immediately postexercise (IPEX) and 9-hours PEX (9hPEX), along with time-matched SED controls. The 9hPEX and their SED-control rats were either refed (RF) or not-refed (NRF). Muscles were analyzed for glycogen and phosphorylation and abundance of key metabolic proteins. Muscles injected with shRNA-GS1 vs shRNA-Scr had lower GS1 abundance in all groups. Regardless of genotype, in IPEX vs SED rats: glycogen fell to similarly low values and phosphorylation of AMPK Thr172 (pAMPK) and its substrate ACC Ser79 (pACC) were comparably increased. Muscle glycogen was increased in all groups of 9h-RF rats, but it was lower for shRNA-GS1 vs shRNA-Scr from RF-9hPEX rats. In the NRF-9hPEX rats, pAMPK and pACC were greater for shRNA-GS1 vs shRNA-Scr muscles. Muscle pyruvate dehydrogenase kinase-4 abundance from 9hPEX rats (both NRF and RF) was greater for shRNA-GS1 vs shRNA-Scr. Hexokinase II (HKII) abundance was greater for 9hPEX vs SED in NRF rats regardless of genotype. In RF-9hPEX rats, HKII abundance was greater for shRNA-GS1 vs shRNA-Scr. These results support the idea that some PEX effects on metabolic protein abundance are influenced by muscle GS1 abundance and the extent of glycogen resynthesis


S.Kwak: None. A.Zheng: None. E.B.Arias: None. H.Wang: None. X.Pan: None. D.Duan: None. Y.Yue: None. G.D.Cartee: None.


National Institutes of Health (R01DK071771); University of Michigan

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at