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1 Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
2 Diabetes and Metabolism Unit, Boston University Hospital, and Research Division, Boston, MA, USA
3 Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
4 Department of Surgery, Ersta Hospital, Karolinska Institutet, Stockholm, Sweden
5 Neurotec, Karolinska Institutet, Stockholm, Sweden
6 Diagnostic Radiology, Karolinska Institutet, Stockholm, Sweden
7 Medicine, Karolinska Institutet, Stockholm, Sweden
* To whom correspondence should be addressed. E-mail: jeanette.kuhl{at}molmed.ki.se.
The study was designed to evaluate whether changes in malonyl CoA and the enzymes that govern its concentration occur in human muscle as a result of physical training. Healthy middle-aged subjects were studied before and after a 12 week training program that increased significantly VO2 max by 13% and decreased intraabdominal fat by 17%. Significant decreases (25-30%) in the concentration of malonyl CoA were observed after training, 24-36 hours following the last bout of exercise. They were accompanied by increases in both the activity (88%) and mRNA (51%) of malonyl CoA decarboxylase (MCD), in muscle, but no changes in the phosphorylation of AMP-Kinase (AMPK) (Thr 172) or of acetyl CoA carboxylase (ACC). The abundance of peroxisomal-proliferator-activated receptor
co-activator 1
(PGC-1
), a regulator of transcription that has been linked to the mediation of MCD expression by PPAR
, was also increased (3-fold). In studies also conducted 24-36h after the last bout of exercise, no evidence of increased whole-body insulin sensitivity or fatty acid oxidation was observed during an euglycemic hyper-insulinemic clamp. In conclusion, the concentration of malonyl CoA is diminished in muscle after physical training, most likely due to PGC1
mediated increases in MCD expression and activity. These changes persist after the increases in AMPK activity and whole-body insulin sensitivity and fatty-acid oxidation, typically caused by an acute bout of exercise in healthy individuals, have dissipated.
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