Aim: 

3,5,3'-L-triiodothyronine (T3) stimulates metabolic rate in many tissues, and induces changes in fuel use through not fully clarified pathways. We studied the involvement of AMP-activated protein kinase (AMPK) and Akt /PKB in these processes.

Methods: 

Rats rendered hypothyroid (by treatment with 6-n-propyl-2-thiouracil and iopanoic acid) were administered a single dose of T3 (25 micrograms/100 g BW), and AMPK and Akt phosphorylation in relation to target proteins was analysed in gastrocnemius muscle at 0, 6, 12, 24, and 48 h after injection.

Results: 

Gastrocnemius muscle displayed a rapid, transient induction (within 6 h) of AMPK phosphorylation (threonine 172) and consequential increases in mitochondrial fatty acid oxidation and carnitine palmitoyl transferase (CPT) activity. At the same time, T3 stimulated signaling toward increased glycolysis through a rapid, persistent increase in Akt/PKB (serine 473) phosphorylation, and a directly related increase in the activity of phosphofructokinase (PFK). There was a concomitant AMPK and Akt-dependent transclocation of glucose transporter 4 (GLUT4) to the membrane and a decline in myosin heavy chain Ib (MHCIb) protein [causing a shift toward the fast-twitch (glycolytic) phenotype].

Conclusion: 

These data show that T3 induces rapid signaling through immediate-early activators of both fatty acid and glucose metabolism (AMPK and Akt/PKB) in skeletal muscle in vivo.