Long-term treatment with the pan-PPAR agonist tetradecylthioacetic acid or fish oil is associated with increased cardiac content of n-3 fatty acids in rat

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.

Cloning and characterization of SREBP-1 and PPAR-α in Japanese seabass Lateolabrax japonicus, and their gene expressions in response to different dietary fatty acid profiles

“…The diets enriched with n−3 PUFA, in particular C18:3n − 3, significantly up-regulated the PPAR-α2 transcript level compared to diets enriched with monounsaturated fatty acids. This was consistent with the stimulation of mammalian PPAR-α by PUFA, in particular C18:3n − 3 (Sekiya et al, 2003;Gani, 2008;Harnack et al, 2009;Hajjar et al, 2012;Lee and Song, 2012;Schmidt et al, 2012;Strand et al, 2012;Devarshi et al, 2013). PPAR-α2 of Japanese seabass was possibly primarily involved in fatty acid oxidation, as have been demonstrated in mammals.…”

PPARs: Protectors or Opponents of Myocardial Function?

“…Long-term treatment of rats with the pan-PPAR agonist tetradecylthioacetic acid (TTA) changes FA composition, including a decrease in saturated fat and arachidonic acid and an increase in n-3 PUFA [ 140 ]. Treatment of mice with TTA for 8 days increased FAO and decreased glucose oxidation, increased myocardial contractility, and reduced cardiac efficiency [ 141 ].…”

Krill oil reduces plasma triacylglycerol level and improves related lipoprotein particle concentration, fatty acid composition and redox status in healthy young adults - a pilot study

“…The total fatty acid composition was analysed in RBC and in EDTA-plasma, as previously described [ 56 ].…”