Diabetes or peroxisome proliferator-activated receptor alpha agonist increases mitochondrial thioesterase I activity in heart.

Abstract:

:Peroxisome proliferator-activated receptor alpha (PPAR alpha) is a transcriptional regulator of the expression of mitochondrial thioesterase I (MTE-I) and uncoupling protein 3 (UCP3), which are induced in the heart at the mRNA level in response to diabetes. Little is known about the regulation of protein expression of MTE-I and UCP3 or about MTE-I activity; thus, we investigated the effects of diabetes and treatment with a PPAR alpha agonist on these parameters. Rats were either made diabetic with streptozotocin (55 mg/kg ip) and maintained for 10-14 days or treated with the PPAR alpha agonist fenofibrate (300 mg/kg/day) for 4 weeks. MTE-I and UCP3 protein expression, MTE-1 activity, palmitate export, and oxidative phosphorylation were measured in isolated cardiac mitochondria. Diabetes and fenofibrate increased cardiac MTE-I mRNA, protein, and activity ( approximately 4-fold compared with controls). This increase in activity was matched by a 6-fold increase in palmitate export in fenofibrate-treated animals, despite there being no effect in either group on UCP3 protein expression. Both diabetes and fenofibrate caused significant decreases in state III respiration of isolated mitochondria with pyruvate + malate as the substrate, but only diabetes reduced state III rates with palmitoylcarnitine. Both diabetes and specific PPAR alpha activation increased MTE-I protein, activity, and palmitate export in the heart, with little effect on UCP3 protein expression.

journal_name

J Lipid Res

authors

King KL,Young ME,Kerner J,Huang H,O'Shea KM,Alexson SE,Hoppel CL,Stanley WC

doi

10.1194/jlr.M600364-JLR200

subject

Has Abstract

pub_date

2007-07-01 00:00:00

pages

1511-7

issue

7

eissn

0022-2275

issn

1539-7262

pii

M600364-JLR200

journal_volume

48

pub_type

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