Aim: 

3,5-diiodo-L-thyronine (T2) enhances fatty acid oxidation and thermogenesis in skeletal muscle (SKM), thus suggesting a potential role of this iodothyronine in protecting SKM from lipotoxicity. In SKM, FAT/CD36 plays a crucial role in the lipid metabolism, as its subcellular redistribution from endosomal compartment to the sarcolemma and to the mitochondria modulates cell free fatty acids (FFA) import and their oxidation rate, respectively.

Methods: 

We investigated on the mechanism by which T2 affects SKM fatty acid metabolism. We tested the ability of T2 to affect i) the translocation of FAT/CD36 to plasma membrane and mitochondria in SKM cells, ii) serum and SKM FFA levels, iii) SKM triglycerides content.

Results: 

Within 1 hour from its injection to hypothyroid rats, T2 promotes FAT/CD36 translocation to sarcolemma and to mitochondria, reduces SKM FFA (-40%), enhances SKM triglyceride content (+10%), suggesting that in the first hour of T2 action FFA imported into the cells are channelled to triglyceride storage and to mitochondrial oxidation. Chronic administration of T2 reduces FFA serum level (-63%) and SKM triglyceride (-40%). This can be explained by the constant higher capacity of SKM to import and to oxidise FFA (revealed by persistently higher sarcolemmal and mitochondrial FAT/CD36 levels).

Conclusion: 

The translocation of FAT/CD36 to sarcolemma and to mitochondria contributes to the up-regulation of SKM lipid metabolism induced by T2 in hypothyroid rats.