Peroxisomal proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) enhances the thyroid hormone induction of carnitine palmitoyltransferase I (CPT-I alpha).
Carnitine palmitoyltransferase I (CPT-I) catalyzes the rate-controlling step in the pathway of mitochondrial fatty acid oxidation. Thyroid hormone will stimulate the expression of the liver isoform of CPT-I (CPT-I alpha). This induction of CPT-I alpha gene expression requires the thyroid hormone response element in the promoter and sequences within the first intron. The peroxisomal proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) is a coactivator that promotes mitochondrial biogenesis, mitochondrial fatty acid oxidation, and hepatic gluconeogenesis. In addition, PGC-1 alpha will stimulate the expression of CPT-I alpha in primary rat hepatocytes. Here we report that thyroid hormone will increase PGC-1 alpha mRNA and protein levels in rat hepatocytes. In addition, overexpression of PGC-1 alpha will enhance the thyroid hormone induction of CPT-I alpha indicating that PGC-1 alpha is a coactivator for thyroid hormone. By using chromatin immunoprecipitation assays, we show that PGC-1 alpha is associated with both the thyroid hormone response element in the CPT-I alpha gene promoter and the first intron of the CPT-I alpha gene. Our data demonstrate that PGC-1 alpha participates in the stimulation of CPT-I alpha gene expression by thyroid hormone and suggest that PGC-1 alpha is a coactivator for thyroid hormone.
Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
Yi
Y
Zhang
Ke
K
Ma
Shulan
S
Song
Marshall B
MB
Elam
George A
GA
Cook
Edwards A
EA
Park
D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004790:Enzyme Induction / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D007163:Immunosorbent Techniques; D007438:Introns / Q000235:genetics; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008156:Luciferases / Q000235:genetics; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D020218:Response Elements / Q000235:genetics; D047488:Retinoid X Receptors / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014284:Triiodothyronine / Q000494:pharmacology*
D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D047488:Retinoid X Receptors; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D014284:Triiodothyronine; D008156:Luciferases; D002334:Carnitine O-Palmitoyltransferase