Peroxisome Proliferator-Activated Receptor Activation is Associated with Altered Plasma One-Carbon Metabolites and B-Vitamin Status in Rats

Nutrients

Vegard Lysne¹  Elin Strand¹  Gard F. T. Svingen¹  Bodil Bjørndal¹  Eva R. Pedersen¹  Øivind Midttun²  Thomas Olsen¹  Per M. Ueland¹  Rolf K. Berge¹ 

[1] Department of Clinical Science, University of Bergen, 5020 Bergen, Norway;Bevital AS, 5021 Bergen, Norway;

关键词: dimethylglycine;    methylmalonic acid;    one-carbon metabolism;    peroxisome proliferator-activated receptors;    tetradecylthioacetic acid;   

DOI  :  10.3390/nu8010026

来源: mdpi

【 摘 要 】

Plasma concentrations of metabolites along the choline oxidation pathway have been linked to increased risk of major lifestyle diseases, and peroxisome proliferator-activated receptors (PPARs) have been suggested to be involved in the regulation of key enzymes along this pathway. In this study, we investigated the effect of PPAR activation on circulating and urinary one-carbon metabolites as well as markers of B-vitamin status. Male Wistar rats (n = 20) received for 50 weeks either a high-fat control diet or a high-fat diet with tetradecylthioacetic acid (TTA), a modified fatty acid and pan-PPAR agonist with high affinity towards PPARα. Hepatic gene expression of PPARα, PPARβ/δ and the enzymes involved in the choline oxidation pathway were analyzed and concentrations of metabolites were analyzed in plasma and urine. TTA treatment altered most biomarkers, and the largest effect sizes were observed for plasma concentrations of dimethylglycine, nicotinamide, methylnicotinamide, methylmalonic acid and pyridoxal, which were all higher in the TTA group (all p < 0.01). Hepatic Pparα mRNA was increased after TTA treatment, but genes of the choline oxidation pathway were not affected. Long-term TTA treatment was associated with pronounced alterations on the plasma and urinary concentrations of metabolites related to one-carbon metabolism and B-vitamin status in rats.

【 授权许可】

CC BY   
© 2016 by the authors; licensee MDPI, Basel, Switzerland.