AMPK as a metabolic switch in rat muscle, liver and adipose tissue after exercise

Acta Physiol Scand. 2003 Aug;178(4):435-42. doi: 10.1046/j.1365-201X.2003.01164.x.


An increasing body of evidence has revealed that activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK)-activated protein kinase increases fatty acid oxidation by lowering the concentration of malonyl coenzyme A (CoA), an inhibitor of carnitine palmitoyl transferase 1. Studies carried out primarily in skeletal muscle suggest that AMPK modulates the concentration of malonyl CoA by concurrently phosphorylating and inhibiting acetyl CoA carboxylase (ACC), the rate limiting enzyme in malonyl CoA synthesis, and phosphorylating and activating malonyl CoA decarboxylase (MCD), an enzyme involved in its degradation. We have recently observed that AMPK and MCD activities are increased and ACC activity diminished in skeletal muscle, liver and, surprisingly, in adipose tissue 30 min following exercise (treadmill run) in normal rats. In liver and adipose tissue these changes were associated with a decrease in the activity of glycerol-3-phosphate acyltransferase (GPAT), which catalyses the first committed reaction in glycerolipid synthesis and, which like ACC, is phosphorylated and inhibited by AMPK. Similar changes in ACC, MCD and GPAT were observed following the administration of 5-aminoimidazole 4-carboxamide-riboside (AICAR), further indicating that the exercise-induced alterations in these enzymes were AMPK-mediated.

Conclusions: (1) AMPK plays a major role in regulating lipid metabolism in multiple tissues following exercise. (2) The net effect of its activation is to increase fatty acid oxidation and diminish glycerolipid synthesis. (3) The relevance of these findings to the regulation of muscle glycogen repletion in the post-exercise state and to the demonstrated ability of AMPK activation to decrease adiposity and increase insulin sensitivity in rodents remains to be determined.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Acetyl-CoA Carboxylase / metabolism
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism*
  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Glycerol-3-Phosphate O-Acyltransferase / metabolism
  • Hypoglycemic Agents / pharmacology
  • Liver / drug effects
  • Liver / metabolism*
  • Malonyl Coenzyme A / metabolism
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Physical Conditioning, Animal / physiology*
  • Rats
  • Ribonucleotides / pharmacology


  • Hypoglycemic Agents
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • Malonyl Coenzyme A
  • Glycerol-3-Phosphate O-Acyltransferase
  • Cyclic AMP-Dependent Protein Kinases
  • Acetyl-CoA Carboxylase
  • AICA ribonucleotide