Effects of chronic AICAR treatment on fiber composition, enzyme activity, UCP3, and PGC-1 in rat muscles

Abstract

This study was designed to determine the histological and metabolic effects of the administration of 5'-AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) for 14 successive days. AICAR treatment caused a significant decrease in the percentage of type IIB fibers and the concomitant increase in the percentage of type IIX fibers in extensor digitorum longus (EDL) muscle. The capillary density and the capillary-to-fiber ratio were not altered by AICAR. AICAR treatment increased the glycolytic and oxidative enzyme activities but not the antioxidant enzyme activities. The AICAR treatment increased the uncoupling protein 3 (UCP3) level in EDL and the peroxisome proliferator-activated receptor-gamma coactivator-1alpha protein level in the soleus and EDL muscles, whereas the myogenin level was not altered by AICAR. These results seem to imply that the chronic activation of AMPK alters such muscle histochemical and metabolic characteristics.

Cold-induced PGC-1α expression modulates muscle glucose uptake through an insulin receptor/Akt-independent, AMPK-dependent pathway

“…Pharmacological and exercise-induced activation of AMPK has been reported to lead to stimulation of PGC-1␣ and UCP-3 protein expression (32,38,39,50). Thus, according to current concepts, PGC-1␣ is a downstream target of AMPK.…”

“…Hyperexpression of PGC-1␣ in muscle cells significantly induces the expression of glucose transporter-4 (GLUT4), but this seems to be an insulin-independent process (22). On the other hand, PGC-1␣ expression is upregulated by endurance training and by chronic treatment with the AMP-activated protein kinase (AMPK) agonist 5-aminoimidazole-4-carboxamide-1-␤-D-ribofuranoside, which lead to increased glucose uptake through insulin-independent mechanisms (1,38).…”

The hitchhiker’s guide to PGC-1α isoform structure and biological functions

“…For this reason, cells keep tight control over PGC-1α activity through diverse transcriptional and post-translational mechanisms. Some of the signalling pathways controlling PGC-1α gene expression involve calcium signalling [12], calcineurin A [13], cyclic AMP [14] and 5′ AMP-activated protein kinase (AMPK) [15]. Activation of these pathways results in the mobilisation of different transcription factors to PGC-1α gene regulatory regions, in a context-and tissue-specific manner.…”

Naturally occurring R225W mutation of the gene encoding AMP-activated protein kinase (AMPK)γ3 results in increased oxidative capacity and glucose uptake in human primary myotubes

“…AMPK may also be regulated through the glycogenbinding domain on the β subunit by the content and structure of intracellular glycogen [9]. When stimulated, AMPK acts to restore cellular energy balance by stimulating ATP-producing pathways (glucose uptake, fatty acid oxidation and mitochondrial biogenesis) [10][11][12][13] and inhibiting ATP-consuming pathways (fatty acid synthesis, glycogen synthesis and protein synthesis) [14][15][16][17].…”