Objective: FAT/CD36 is involved in skeletal muscle (SkM) fatty acid (FA) utilization. In case of increased energy demand, the capacity of SkM to rapidly modulate the uptake of FA and their successive oxidation can be increased by translocation of FAT/CD36 from intracellular pools to the sarcolemma and to mitochondria. 3,5-diiodo-l-thyronine (T2) enhances energy expenditure and fatty acid metabolism in SkM and we hypothesized that related changes in lipid handling would occur due by FAT/CD36 redistribution within the cell.

Methods: We evaluated the subcellular distribution of FAT/CD36 in gastrocnemius muscles of T2-treated rats by immunohistochemistry. We also used an in vitro model of skeletal fibers (C2C12 cell line) to study FAT/CD36 cell redistribution by immunocytochemistry and confocal miscroscopy.

Results: The "in vivo" administration of T2 to rats enhanced FAT/CD36 immunoreactivity in sarcolemma but also in subsarcolemmal regions of the skeletal fiber. The fluorescence immunocytochemistry showed that within 1 hour from its "in vitro" addition to C2C12 cells, T2 enhances FAT/CD36 sarcolemmal punctate staining. In addition, FAT/CD36 colocalized with mitochondrial dye Mitotracker Red only when cells were incubated with T2 and not in control cells, thus demonstrating that T2 induces a strictly association between FAT/CD36 and muscle mitochondria.

Conclusion: FAT/CD36 subcellular redistribution could underlie the enhancement of SkM FA utilization induced by T2 administration.