3,5-diiodo-L-thyronine (T2) is able to increase metabolic rate of hypothyroid rats and to decrease both body weight gain and fat accumulation when injected into high fat diet fed rats. This suggests that T2 could i) address lipid partition toward oxidation, ii) stimulate mitochondrial thermogenesis.

Aim: 

We investigated on the ability of T2 to rapidly influence both skeletal muscle mitochondrial substrates oxidation and thermogenesis, when injected into hypothyroid rats.

Methods: 

Rats were made hypothyroid by propyl-thiouracil and iopanoic acid treatment for 4 week. T2 (25 mg/100 g bw) or saline were injected into hypothyroid rats 1 hour before the sacrifice.

Results: 

Within 1 hour from its injection, T2 enhanced mitochondrial palmitoyl-CoA, palmitoyl-carnitine and succinate oxidation rates. However, T2 did not affect piruvate oxidation. T2 rapidly activated AMPK-ACC-Malonyl-CoA metabolic signalling pathway, known to direct lipid partition towards oxidation. Along with these effects, T2 enhanced proton-leak kinetics, thus, activating mitochondrial thermogenesis.

Conclusion: 

T2 enhances mitochondrial fatty acid oxidation and thermogenesis. By activating these processes T2 could play crucial roles in a) protecting skeletal muscle against excessive intramyocellular lipid storage and lipotoxicity and b) avoiding metabolic disorders.