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.
BACKGROUND
Excess 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.


RESULTS
After 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.


CONCLUSIONS
Long-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.
Institute of Medicine, University of Bergen, Haukeland University Hospital, Laboratory Building 8th floor, 5021 Bergen, Norway. Elin.Strand@med.uib.no
Elin
E
Strand
Bodil
B
Bjorndal
Ottar
O
Nygard
Lena
L
Burri
Christ
C
Berge
Pavol
P
Bohov
Bjørn J
BJ
Christensen
Kjetil
K
Berge
Hege
H
Wergedahl
Asgaut
A
Viste
Rolf K
RK
Berge
D042962:Acyl-CoA Oxidase / Q000378:metabolism; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005395:Fish Oils / Q000008:administration & dosage* / Q000494:pharmacology; D015870:Gene Expression; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D009928:Organ Specificity; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000008:administration & dosage* / Q000494:pharmacology; D013997:Time Factors; D000071247:Uncoupling Protein 3
D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047492:Peroxisome Proliferator-Activated Receptors; D013440:Sulfides; C000604394:Ucp3 protein, rat; D000071247:Uncoupling Protein 3; C062078:1-(carboxymethylthio)tetradecane; D042962:Acyl-CoA Oxidase; D005992:Glycerol-3-Phosphate O-Acyltransferase; D002334:Carnitine O-Palmitoyltransferase