Responses of skeletal muscle lipid metabolism in rat gastrocnemius to hypothyroidism and iodothyronine administration: a putative role for FAT/CD36.

Iodothy-ronines such as triiodothyronine (T₃) and 3,5-diiodothyronine (T₂) influence energy expenditure and lipid metabolism. Skeletal muscle contributes significantly to energy homeostasis, and the above iodo-thyronines are known to act on this tissue. However, little is known about the cellular/molecular events underlying the effects of T₃ and T₂ on skeletal muscle lipid handling. Since FAT/CD36 is involved in the utilization of free fatty acids by skeletal muscle, specifically in their import into that tissue and presumably their oxidation at the mito-chondrial level, we hypothesized that related changes in lipid handling and in FAT/CD36 expression and subcellular redistribution would occur due to hypothyroidism and to T₃ or T₂ administration to hypothyroid rats. In gastrocnemius muscles isolated from hypothyroid rats, FAT/CD36 was upregulated (mRNA levels and total tissue, sarcolemmal, and mitochondrial protein levels). Administration of either T₃ or T₂ to hypothyroid rats resulted in 1) little or no change in FAT/CD36 mRNA level, 2) a decreased total FAT/CD36 protein level, and 3) further increases in FAT/CD36 protein level in sarco-lemma and mitochondria. Thus, the main effect of each iodothyronine seemed to be exerted at the level of FAT/CD36 cellular distribution. The effect of further increases in FAT/CD36 protein level in sarco-lemma and mitochondria was already evident at 1 h after iodothyro-nine administration. Each iodothyronine increased the mitochondrial fatty acid oxidation rate. However, the mechanisms underlying their rapid effects seem to differ; T₂ and T₃ each induce FAT/CD36 translocation to mitochondria, but only T₂ induces increases in car-nitine palmitoyl transferase system activity and in the mitochondrial substrate oxidation rate. [ABSTRACT FROM AUTHOR]