Exercise training decreases the concentration of malonyl-CoA and increases the expression and activity of malonyl-CoA decarboxylase in human muscle.
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 VO2 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, Thr172) or of acetyl-CoA carboxylase. The abundance of peroxisome proliferator-activated receptor (PPAR)gamma coactivator-1alpha (PGC-1alpha), a regulator of transcription that has been linked to the mediation of MCD expression by PPARalpha, 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-1alpha-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.
Kuhl
Jeanette E
JE
Dept. of Molecular Medicine and Surgery, Karolinska Institutet, S-171 76 Stockholm, Sweden. jeanette.kuhl@molmed.ki.se
Ruderman
Neil B
NB
Musi
Nicolas
N
Goodyear
Laurie J
LJ
Patti
Mary Elizabeth
ME
Crunkhorn
Sarah
S
Dronamraju
Deepti
D
Thorell
Anders
A
Nygren
Jonas
J
Ljungkvist
Olle
O
Degerblad
Marie
M
Stahle
Agneta
A
Brismar
Torkel B
TB
Andersen
Kirstine L
KL
Saha
Asish K
AK
Efendic
Suad
S
Bavenholm
Peter N
PN
D000091162:AMP-Activated Protein Kinase Kinases; D002262:Carboxy-Lyases / Q000378:metabolism*; D003430:Cross-Sectional Studies; D015444:Exercise; D005260:Female; D006801:Humans; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism*; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D020675:Peroxisomes; D011494:Protein Kinases / Q000378:metabolism
D047495:PPAR gamma; D008316:Malonyl Coenzyme A; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D002262:Carboxy-Lyases; C021532:malonyl-CoA decarboxylase