title: Tetradecylthioacetic acid increases fat metabolism and improves cardiac function in experimental heart failure.
abstract: Changes in myocardial metabolism, including a shift from fatty acid to glucose utilization and changes in fatty acid availability and composition are characteristics of heart failure development. Tetradecylthioacetic acid (TTA) is a fatty acid analogue lacking the ability to undergo mitochondrial β-oxidation. TTA promotes hepatic proliferation of mitochondria and peroxisomes and also decreases serum triglycerides and cholesterol in animals. We investigated the effect of TTA, in combination with a high-fat or regular diet, in a rat model of post-myocardial infarction heart failure. TTA had a beneficial effect on cardiac function in post-myocardial infarction heart failure without affecting myocardial remodeling. These effects of TTA on myocardial function were accompanied by decreased free fatty acids in plasma, increased myocardial proportion of n-3 polyunsaturated fatty acids (PUFA) and a decreased proportion of n-6 PUFA. Myocardial enzyme gene expression during TTA treatment suggested that the increase in n-3 PUFA could reflect increased n-3 PUFA synthesis and inadequately increased n-3 PUFA β-oxidation. Based on our data, it is unlikely that the changes are secondary to alterations in other tissues as plasma and liver showed an opposite pattern with decreased n-3 PUFA during TTA treatment. The present study suggests that TTA may improve myocardial function in heart failure, potentially involving its ability to decrease the availability of FFA and increase the myocardial proportion of n-3 PUFA.
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway.
authors.forename: Erik
authors.initials: E
authors.lastname: Øie
authors.forename: Rolf K
authors.initials: RK
authors.lastname: Berge
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Christen P
authors.initials: CP
authors.lastname: Dahl
authors.forename: Thor
authors.initials: T
authors.lastname: Edvardsen
authors.forename: Jan Otto
authors.initials: JO
authors.lastname: Beitnes
authors.forename: Pavol
authors.initials: P
authors.lastname: Bohov
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D005223:Fats / Q000032:analysis / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000032:analysis / Q000097:blood / Q000378:metabolism; D043371:Fatty Acids, Omega-6 / Q000032:analysis / Q000097:blood / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000150:complications; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D005223:Fats; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D008055:Lipids; D013440:Sulfides; C062078:1-(carboxymethylthio)tetradecane