Abstract
BackgroundExcess peroxisome proliferator-activated receptor (PPAR) stimulation has been associated with detrimental health effects including impaired myocardial function. Recently, supplementation with n-3 polyunsaturated fatty acids (PUFA) has been associated with improved left ventricular function and functional capacity in patients with dilated cardiomyopathy. We investigated the long-term effects of the pan-PPAR agonist tetradecylthioacetic acid (TTA) and/or high-dose fish oil (FO) on cardiac fatty acid (FA) composition and lipid metabolism. Male Wistar rats were given one out of four different 25% (w/v) fat diets: control diet; TTA diet; FO diet; or diet containing both TTA and FO.ResultsAfter 50 weeks n-3 PUFA levels were increased by TTA and FO in the heart, whereas liver levels were reduced following TTA administration. TTA was associated with a decrease in arachidonic acid, increased activities of carnitine palmitoyltransferase II, fatty acyl-CoA oxidase, glycerol-3-phosphate acyltransferase, and fatty acid synthase in the heart. Furthermore, cardiac Ucp3 and Cact mRNA was upregulated.ConclusionsLong-term treatment with the pan-PPAR agonist TTA or high-dose FO induced marked changes in PUFA composition and enzymatic activity involved in FA metabolism in the heart, different from liver. Changes included increased FA oxidation and a selective increase in cardiac n-3 PUFA.
Highlights
Excess peroxisome proliferator-activated receptor (PPAR) stimulation has been associated with detrimental health effects including impaired myocardial function
To eliminate the possibility of an effect-modification caused by the jejuno-gastric reflux surgical procedure, changes in body weight and plasma lipids were studied in an 11 week pilot study
The activity of enzymes involved in fatty acid (FA) metabolism were changed in the heart after tetradecylthioacetic acid (TTA) treatment, including increased carnitine palmitoyltransferase II (CPT-II), acyl-Coenzyme A (CoA) oxidase (ACOX), glycerol-3-phosphate acyltransferase (GPAT), and fatty acid synthase (FAS) activities as well as a significant upregulation of uncoupling protein 3 (Ucp3) and carnitine-acylcarnitine translocase (Cact) at the mRNA level
Summary
Excess peroxisome proliferator-activated receptor (PPAR) stimulation has been associated with detrimental health effects including impaired myocardial function. A diet rich in n-3 polyunsaturated FA (PUFA) like eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3), has been associated with reduced triacylglycerol (TAG) levels, anti-inflammatory effects, and a lowered risk of cardiovascular disease and mortality [10,11]. These beneficial effects may be less evident in patients with stable angina [12,13], but pronounced in patients with reduced ventricular function and heart failure [14]. Very high doses of n-3 PUFA could, be pro-inflammatory and prooxidative [15]
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