title: Carnitine palmitoyl transferase-I inhibition is not associated with cardiac hypertrophy in rats fed a high-fat diet.
abstract: 1. Cardiac lipotoxicity is characterized by hypertrophy and contractile dysfunction and can be triggered by impaired mitochondrial fatty acid oxidation and lipid accumulation. The present study investigated the effect of dietary fatty acid intake alone and in combination with inhibition of mitochondrial fatty acid uptake with the carnitine palmitoyl transferase (CPT)-I inhibitor oxfenicine. Long-chain fatty acids activate peroxisome proliferator-activated receptors (PPAR), thus mRNA levels of PPAR target genes were measured. 2. Rats were untreated or given the CPT-I inhibitor oxfenicine (150 mg/kg per day) and were fed for 8 weeks with either: (i) standard low-fat chow (10% of energy from fat); (ii) a long-chain saturated fatty acid diet; (iii) a long-chain unsaturated fatty acid diet; or (iv) a medium-chain fatty acid diet (which bypasses CPT-I). High-fat diets contained 60% of energy from fat. 3. Cardiac triglyceride content was increased in the absence of oxfenicine in the saturated fat group compared with other diets. Oxfenicine treatment further increased cardiac triglyceride stores in the saturated fat group and caused a significant increase in the unsaturated fat group. Despite elevations in triglyceride stores, left ventricular mass, end diastolic volume and systolic function were unaffected. 4. The mRNA levels of PPAR-regulated genes were increased by the high saturated and unsaturated fat diets compared with standard chow or the medium chain fatty acid chow. Oxfenicine did not further upregulate PPARalpha target genes within each dietary treatment group. 5. Taken together, the data suggest that consuming a high-fat diet or inhibiting CPT-I do not result in cardiac hypertrophy or cardiac dysfunction in normal rats.
authors.affiliation: Department of Physiology, Case Western Reserve University, Cleveland, Ohio 44106-4970, USA.
authors.forename: Isidore C
authors.initials: IC
authors.lastname: Okere
authors.forename: Margaret P
authors.initials: MP
authors.lastname: Chandler
authors.forename: Tracy A
authors.initials: TA
authors.lastname: McElfresh
authors.forename: Julie H
authors.initials: JH
authors.lastname: Rennison
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Kung
authors.forename: Brian D
authors.initials: BD
authors.lastname: Hoit
authors.forename: Paul
authors.initials: P
authors.lastname: Ernsberger
authors.forename: Martin E
authors.initials: ME
authors.lastname: Young
authors.forename: William C
authors.initials: WC
authors.lastname: Stanley
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D007473:Ion Channels / Q000235:genetics; D020738:Leptin / Q000097:blood; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics; D009206:Myocardium / Q000378:metabolism; D047493:PPAR alpha / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood; D000071247:Uncoupling Protein 3
chemical_list: D004041:Dietary Fats; D004791:Enzyme Inhibitors; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007473:Ion Channels; D020738:Leptin; D024101:Mitochondrial Proteins; D047493:PPAR alpha; D012333:RNA, Messenger; D014280:Triglycerides; D000071247:Uncoupling Protein 3; C023010:4-hydroxyphenylglycine; D042964:Acyl-CoA Dehydrogenase; D002334:Carnitine O-Palmitoyltransferase; D002950:Citrate (si)-Synthase; D011494:Protein Kinases; C403287:pyruvate dehydrogenase kinase 4; D005998:Glycine