Short-term treatment with a peroxisome proliferator-activated receptor α agonist influences plasma one-carbon metabolites and B-vitamin status in rats

PLoS One. 2019 Dec 5;14(12):e0226069. doi: 10.1371/journal.pone.0226069. eCollection 2019.

Abstract

Introduction: Peroxisome proliferator-activated receptors (PPARs) have been suggested to be involved in the regulation of one-carbon metabolism. Previously we have reported effects on plasma concentrations of metabolites along these pathways as well as markers of B-vitamin status in rats following treatment with a pan-PPAR agonist. Here we aimed to investigate the effect on these metabolites after specific activation of the PPARα and PPARγ subtypes.

Methods: For a period of 12 days, Male Wistar rats (n = 20) were randomly allocated to receive treatment with the PPARα agonist WY-14.643 (n = 6), the PPARγ agonist rosiglitazone (n = 6) or placebo (n = 8). The animals were sacrificed under fasting conditions, and plasma concentration of metabolites were determined. Group differences were assessed by one-way ANOVA, and planned comparisons were performed for both active treatment groups towards the control group.

Results: Treatment with a PPARα agonist was associated with increased plasma concentrations of most biomarkers, with the most pronounced differences observed for betaine, dimethylglycine, glycine, nicotinamide, methylnicotinamide, pyridoxal and methylmalonic acid. Lower levels were observed for flavin mononucleotide. Fewer associations were observed after treatment with a PPARγ agonist, and the most notable was increased plasma serine.

Conclusion: Treatment with a PPARα agonist influenced plasma concentration of one-carbon metabolites and markers of B-vitamin status. This confirms previous findings, suggesting specific involvement of PPARα in the regulation of these metabolic pathways as well as the status of closely related B-vitamins.

MeSH terms

  • Animals
  • Carbon / metabolism*
  • Male
  • PPAR alpha / agonists*
  • PPAR gamma / agonists
  • Pyrimidines / pharmacology*
  • Rats
  • Rats, Wistar
  • Rosiglitazone / pharmacology
  • Time Factors
  • Vitamin B Complex / blood*

Substances

  • PPAR alpha
  • PPAR gamma
  • Pyrimidines
  • Rosiglitazone
  • Vitamin B Complex
  • Carbon
  • pirinixic acid

Grant support

Authors ØM and PMU are employed by BEVITAL A/S (www.bevital.no), who performed the biochemical analyses for this study. The funder provided support in the form of salaries for authors [ØM and PMU], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.