Increased hepatic pyruvate dehydrogenase kinase activity in fed hyperthyroid rats: studies in vivo and with cultured hepatocytes.
Experimental hyperthyroidism induced by the administration of tri-iodothyronine (T3; 100 micrograms/100 g body wt; 3 days) increased plasma non-esterified fatty acids in the fed state in the rat. At the same time, hepatic PDH kinase responded with a persistent (1.6-fold) increase in activity. The exposure of hepatocytes from fed euthyroid rats to T3 (100 nM) in culture for 21 h increased PDH kinase activity to an extent comparable to that observed in vivo in response to hyperthyroidism. The in vitro increase in PDH kinase activity was suppressed by insulin (100 microU/ml) and by inhibition of mitochondrial fatty acid oxidation. The results demonstrate a direct hepatic action of T3 to increase PDH kinase activity, which is mediated by intramitochondrial fatty acyl-CoA or a product of beta-oxidation, and facilitated by hepatic insulin resistance.
Sugden
M C
MC
Department of Biochemistry, Queen Mary and Westfield College, (University of London), UK.
Fryer
L G
LG
Priestman
D A
DA
Orfali
K A
KA
Holness
M J
MJ
D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003994:Bucladesine / Q000494:pharmacology; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000032:analysis; D004435:Eating; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000494:pharmacology; D006003:Glycogen / Q000032:analysis; D006980:Hyperthyroidism / Q000139:chemically induced / Q000201:enzymology* / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D008099:Liver / Q000737:chemistry / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010168:Palmitates / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000032:analysis; D014284:Triiodothyronine / Q000494:pharmacology
D000214:Acyl Coenzyme A; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010168:Palmitates; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D014280:Triglycerides; D014284:Triiodothyronine; D003994:Bucladesine; D006003:Glycogen; D005934:Glucagon; D000242:Cyclic AMP; D002334:Carnitine O-Palmitoyltransferase; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases