title: Peroxisome Proliferator-Activated Receptor Activation is Associated with Altered Plasma One-Carbon Metabolites and B-Vitamin Status in Rats.
abstract: 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.
authors.affiliation: Department of Clinical Science, University of Bergen, 5020 Bergen, Norway. vegard.lysne@uib.no.
authors.forename: Vegard
authors.initials: V
authors.lastname: Lysne
authors.affiliation: Department of Clinical Science, University of Bergen, 5020 Bergen, Norway. elin.strand@uib.no.
authors.forename: Elin
authors.initials: E
authors.lastname: Strand
authors.affiliation: Department of Clinical Science, University of Bergen, 5020 Bergen, Norway. gard.frodahl.tveitevag.svingen@helse-bergen.no.|Department of Heart Disease, Haukeland University Hospital, 5021 Bergen, Norway. gard.frodahl.tveitevag.svingen@helse-bergen.no.
authors.forename: Gard F T
authors.initials: GF
authors.lastname: Svingen
authors.affiliation: Department of Clinical Science, University of Bergen, 5020 Bergen, Norway. Bodil.Bjorndal@k2.uib.no.
authors.forename: Bodil
authors.initials: B
authors.lastname: Bjørndal
authors.affiliation: Department of Clinical Science, University of Bergen, 5020 Bergen, Norway. eva.pedersen@k2.uib.no.|Department of Heart Disease, Haukeland University Hospital, 5021 Bergen, Norway. eva.pedersen@k2.uib.no.
authors.forename: Eva R
authors.initials: ER
authors.lastname: Pedersen
authors.affiliation: Bevital AS, 5021 Bergen, Norway. Bjorn.Midttun@uib.no.
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Midttun
authors.affiliation: Department of Clinical Science, University of Bergen, 5020 Bergen, Norway. olsen.thomas89@gmail.com.
authors.forename: Thomas
authors.initials: T
authors.lastname: Olsen
authors.affiliation: Department of Clinical Science, University of Bergen, 5020 Bergen, Norway. per.ueland@ikb.uib.no.|Laboratory of Clinical Biochemistry, Haukeland University Hospital, 5021 Bergen, Norway. per.ueland@ikb.uib.no.
authors.forename: Per M
authors.initials: PM
authors.lastname: Ueland
authors.affiliation: Department of Clinical Science, University of Bergen, 5020 Bergen, Norway. Rolf.Berge@uib.no.|Department of Heart Disease, Haukeland University Hospital, 5021 Bergen, Norway. Rolf.Berge@uib.no.
authors.forename: Rolf K
authors.initials: RK
authors.lastname: Berge
authors.affiliation: Department of Clinical Science, University of Bergen, 5020 Bergen, Norway. Ottar.Nygard@helse-bergen.no.|Department of Heart Disease, Haukeland University Hospital, 5021 Bergen, Norway. Ottar.Nygard@helse-bergen.no.|KG Jebsen Centre for Diabetes Research, University of Bergen, 5009 Bergen, Norway. Ottar.Nygard@helse-bergen.no.
authors.forename: Ottar
authors.initials: O
authors.lastname: Nygård
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D002794:Choline / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D015870:Gene Expression; D008099:Liver / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008764:Methylmalonic Acid / Q000097:blood; D009536:Niacinamide / Q000097:blood; D009539:Nicotinic Acids / Q000097:blood; D019875:One-Carbon Group Transferases / Q000097:blood*; D047493:PPAR alpha / Q000235:genetics; D048068:PPAR-beta / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism*; D011730:Pyridoxal / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012521:Sarcosine / Q000031:analogs & derivatives / Q000097:blood; D013440:Sulfides / Q000008:administration & dosage / Q000494:pharmacology*; D014803:Vitamin B Complex / Q000032:analysis*
chemical_list: D000975:Antioxidants; D009539:Nicotinic Acids; D047493:PPAR alpha; D048068:PPAR-beta; D047492:Peroxisome Proliferator-Activated Receptors; D012333:RNA, Messenger; D013440:Sulfides; D014803:Vitamin B Complex; D009536:Niacinamide; D011730:Pyridoxal; C025138:dimethylglycine; C008473:methyl nicotinate; C062078:1-(carboxymethylthio)tetradecane; D008764:Methylmalonic Acid; D019875:One-Carbon Group Transferases; D002794:Choline; D012521:Sarcosine
keywords: dimethylglycine; methylmalonic acid; one-carbon metabolism; peroxisome proliferator-activated receptors; tetradecylthioacetic acid