title: Responses of skeletal muscle lipid metabolism in rat gastrocnemius to hypothyroidism and iodothyronine administration: a putative role for FAT/CD36.
abstract: Iodothyronines such as triiodothyronine (T(3)) and 3,5-diiodothyronine (T(2)) influence energy expenditure and lipid metabolism. Skeletal muscle contributes significantly to energy homeostasis, and the above iodothyronines are known to act on this tissue. However, little is known about the cellular/molecular events underlying the effects of T(3) and T(2) 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 mitochondrial level, we hypothesized that related changes in lipid handling and in FAT/CD36 expression and subcellular redistribution would occur due to hypothyroidism and to T(3) or T(2) 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 T(3) or T(2) 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 sarcolemma 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 sarcolemma and mitochondria was already evident at 1 h after iodothyronine administration. Each iodothyronine increased the mitochondrial fatty acid oxidation rate. However, the mechanisms underlying their rapid effects seem to differ; T(2) and T(3) each induce FAT/CD36 translocation to mitochondria, but only T(2) induces increases in carnitine palmitoyl transferase system activity and in the mitochondrial substrate oxidation rate.
authors.affiliation: Dipartimento delle Scienze Biologiche, Università di Napoli Federico II, Naples, Italy.
authors.forename: Assunta
authors.initials: A
authors.lastname: Lombardi
authors.forename: Rita
authors.initials: R
authors.lastname: De Matteis
authors.forename: Maria
authors.initials: M
authors.lastname: Moreno
authors.forename: Laura
authors.initials: L
authors.lastname: Napolitano
authors.forename: Rosa Anna
authors.initials: RA
authors.lastname: Busiello
authors.forename: Rosalba
authors.initials: R
authors.lastname: Senese
authors.forename: Pieter
authors.initials: P
authors.lastname: de Lange
authors.forename: Antonia
authors.initials: A
authors.lastname: Lanni
authors.forename: Fernando
authors.initials: F
authors.lastname: Goglia
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D002153:Calorimetry, Indirect; D002460:Cell Line; D004104:Diiodothyronines / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism; D007037:Hypothyroidism / Q000097:blood / Q000378:metabolism*; D007150:Immunohistochemistry; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D051379:Mice; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D018955:CD36 Antigens; D004104:Diiodothyronines; D005230:Fatty Acids, Nonesterified; D012333:RNA, Messenger; D014284:Triiodothyronine; C030103:3,5-diiodothyronine