1. Changes in exercise-induced gene expression in 5'-AMP--activated protein kinase γ3-null and γ3 R225Q transgenic mice
- Author
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Barnes, Brian R., Long, Yun Chau, Steiler, Tatiana L., Leng, Ying, Galuska, Dana, Wojtaszewski, Jorgen F.P., Andersson, Leif, and Zierath, Juleen R.
- Subjects
Biological oxidation (Metabolism) -- Health aspects -- Research ,Diabetes -- Risk factors -- Diagnosis -- Care and treatment -- Research ,Protein kinases -- Health aspects -- Research ,Health ,Diagnosis ,Care and treatment ,Research ,Risk factors ,Health aspects - Abstract
5'-AMP-activated protein kinase (AMPK) is important for metabolic sensing. We used AMPKγ3 mutant-overexpressing Tg-Prkag[3.sup.225Q] and AMPKγ3-knockout Prkag[3.sup.-/-] mice to determine the role of the AMPKγ3 isoform in exercise-induced metabolic and gene regulatory responses in skeletal muscle. Mice were studied after 2 h swimming or 2.5 h recovery. Exercise increased basal and insulin-stimulated glucose transport, with similar responses among genotypes. In Tg-Prkag[3.sup.225Q] mice, acetyl-CoA carboxylase (ACC) phosphorylation was increased and triglyceride content was reduced after exercise, suggesting that this mutation promotes greater reliance on lipid oxidation. In contrast, ACC phosphorylation and triglyceride content was similar between wild-type and Prkag[3.sup.-/-] mice. Expression of genes involved in lipid and glucose metabolism was altered by genetic modification of AMPKγ3. Expression of lipoprotein lipase 1, carnitine palmitoyl transferase lb, and 3-hydroxyacyl-CoA dehydrogenase was increased in Tg-Prkag[3.sup.225Q] mice, with opposing effects in Prkag[3.sup.-/-] mice after exercise. GLUT4, hexokinase II (HKII), and glycogen synthase mRNA expression was increased in Tg-Prkag[3.sup.225Q] mice after exercise. GLUT4 and HKII mRNA expression was increased in wild-type mice and blunted in Prkag[3.sup.-/-] mice after recovery. In conclusion, the Prkag[3.sup.225Q] mutation, rather than presence of a functional AMPKγ3 isoform, directly promotes metabolic and gene regulatory responses along lipid oxidative pathways in skeletal muscle after endurance exercise., 5'-AMP--activated protein kinase (AMPK) is a cellular energy sensor that responds to alterations in the AMP-to-ATP ratio. Activation of AMPK in response to metabolic stress initiates several signaling cascades aimed [...]
- Published
- 2005