Effects of chronic AICAR administration on the metabolic and contractile phenotypes of rat slow- and fast-twitch skeletal muscles

• Published in: Canadian journal of physiology and pharmacology Vol. 81; no. 11; p. 1072
• Main Authors: Bamford, Jeremy A, Lopaschuk, Gary D, MacLean, Ian M, Reinhart, Marcia L, Dixon, Walter T, Putman, Charles T
• Format: Journal Article
• Language: English
• Published: Canada 01-11-2003
• Subjects: Aminoimidazole Carboxamide - administration & dosage; Aminoimidazole Carboxamide - analogs & derivatives; AMP-Activated Protein Kinases; Animals; Drug Administration Schedule; Enzyme Activation - drug effects; Enzyme Activation - physiology; Male; Multienzyme Complexes - genetics; Multienzyme Complexes - metabolism; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle Fibers, Fast-Twitch - drug effects; Muscle Fibers, Fast-Twitch - enzymology; Muscle Fibers, Fast-Twitch - metabolism; Muscle Fibers, Slow-Twitch - drug effects; Muscle Fibers, Slow-Twitch - enzymology; Muscle Fibers, Slow-Twitch - metabolism; Phenotype; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Rats; Rats, Sprague-Dawley; Ribonucleotides - administration & dosage
• ISSN: 0008-4212
• DOI: 10.1139/y03-110

The present study examined the effects of chronic activation of 5'-AMP-activated protein kinase (AMPK) on the oxidative capacity and myosin heavy chain (MHC) based fibre phenotype of rodent fast- and slow-twitch muscles. Sprague-Dawley rats received daily injections for 4 weeks of the known AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) or vehicle (control). The AICAR group displayed increases in hexokinase-II (HXK-II) activity, expression, and phosphorylation in fast-twitch muscles (P<0.001) but not in the slow-twitch soleus (SOL). In the AICAR group, citrate synthase (EC 4.1.3.7) and 3-hydroxyacyl-CoA-dehydrogenase (EC 1.1.1.35) were elevated 1.6- and 2.1-fold (P<0.05), respectively, in fast-twitch medial gastrocnemius (MG), and by 1.2- and 1.4-fold (P<0.05) in the slower-twitch plantaris (PLANT). No changes were observed in the slow-twitch SOL. In contrast, the activity of glyceraldehyde phosphate dehydrogenase (EC 1.2.1.12) remained unchanged in all muscles. AICAR treatment did not alter the MHC-based fibre type composition in fast- or slow-twitch muscles, as determined by immunohistochemical and electrophoretic analytical methods or by RT-PCR. We conclude that chronic activation of AMPK mimics the metabolic changes associated with chronic exercise training (increased oxidative capacity) in the fast-twitch MG and PLANT, but does not coordinately alter MHC isoform content or mRNA expression.