3,5-diiodothyronines (T2), a thyroid hormone derivative, affects both energy and lipid homeostasis. T2 enhances rat metabolic rate and prevents high fat diet induced obesity, without inducing thyrotoxicosis. T2 can be considered as promising strategy for treating lipid disorders and obesity. To gain further insight into the effects it elicits, we investigated the ability of T2 to influence gastrocnemius skeletal muscle (GSkM) lipid metabolism. We focused our attention on FAT/CD36 in view of the crucial role played in the uptake of free fatty acid into GSkM and its oxidation at the mitochondrial level. We also compared the effects induced by T2 with those of T3.

Hypothyroidism enhanced FAT/CD36 protein content in GSkM lysate, in isolated sarcolemma and mitochondria. The administration of either T2 or T3 to hypothyroid rats reduced FAT/CD36 content in GSkM lysate, while further increasing its sarcolemmal and mitochondrial levels. T2 as well as T3, by promoting the translocation of FAT/CD36 from endocellular depots towards the above compartments, promptly (within 1 hour) enhanced the ability of GSkM to import and to oxidise fatty acids, thus suggesting "non genomic effects ". At the mitochondrial level, FAT/CD36 seems to be the main component responsible for the rapid induction of mitochondrial palmitate oxidation by T3; additional mechanisms involving mitochondrial fatty acids import and respiratory pathways are involved in T2 effects.