Exercise training decreases the concentration of malonyl-CoA and increases the expression and activity of malonyl-CoA decarboxylase in human muscle

• Published in: American journal of physiology: endocrinology and metabolism Vol. 290; no. 6; pp. E1296 - E1303
• Main Authors: Kuhl, Jeanette E, Ruderman, Neil B, Musi, Nicolas, Goodyear, Laurie J, Patti, Mary Elizabeth, Crunkhorn, Sarah, Dronamraju, Deepti, Thorell, Anders, Nygren, Jonas, Ljungkvist, Olle, Degerblad, Marie, Stahle, Agneta, Brismar, Torkel B, Andersen, Kirstine L, Saha, Asish K, Efendic, Suad, Bavenholm, Peter N
• Format: Journal Article
• Language: English
• Published: United States 01.06.2006
• Subjects: Carboxy-Lyases - metabolism; Cross-Sectional Studies; Exercise; Female; Humans; Male; Malonyl Coenzyme A - metabolism; Medicin och hälsovetenskap; Middle Aged; Muscles - metabolism; Peroxisomes; PPAR gamma - metabolism; Protein Kinases - metabolism
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00341.2005

1 Karolinska Institutet, Molecular Medicine and Surgery, Stockholm, Sweden; 2 Boston University Hospital, Research Division, Diabetes and Metabolism Unit; 3 Harvard Medical School, Joslin Diabetes Center, Boston, Massachusetts; 4 Karolinska Institutet, Department of Surgery, Ersta Hospital; 5 Karolinska Institutet, Neurotec; 6 Karolinska Institutet, Diagnostic Radiology; and 7 Karolinska Institutet, Medicine, Stockholm, Sweden Submitted 27 July 2005 ; accepted in final form 18 January 2006 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-wk training program that significantly increased O 2 max by 13% and decreased intra-abdominal fat by 17%. Significant decreases (25–30%) in the concentration of malonyl-CoA were observed after training, 24–36 h after 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. The abundance of peroxisome proliferator-activated receptor (PPAR) coactivator-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 24–36 h after the last bout of exercise, no evidence of increased whole body insulin sensitivity or fatty acid oxidation was observed during an euglycemic hyperinsulinemic clamp. In conclusion, the concentration of malonyl-CoA is diminished in muscle after physical training, most likely because of PGC-1 -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. insulin sensitivity; adenosine 5'-monophosphate kinase; acetyl-coenzyme A carboxylase; peroxisome proliferator-activated receptor- coactivator-1 Address for reprint requests and other correspondence: J. Kuhl, Dept. of Molecular Medicine and Surgery, Karolinska Institutet, S-171 76 Stockholm, Sweden (e-mail: jeanette.kuhl{at}molmed.ki.se )