title: Dietary proanthocyanidins modulate BMAL1 acetylation, Nampt expression and NAD levels in rat liver.
abstract: Metabolism follows circadian rhythms, which are driven by peripheral clocks. Clock genes in the liver are entrained by daytime meals and food components. Proanthocyanidins (PAs), the most abundant flavonoids in the human diet, modulate lipid and glucose metabolism. The aim of this study was to determine whether PAs could adjust the clock system in the liver. Male Wistar rats were orally gavaged with 250 mg grape seed proanthocyanidin extract (GSPE)/kg body weight at zeitgeber time (ZT) 0 (light turned on), at ZT12 (light turned off), or before a 6 hour jet-lag and sacrificed at different times. The 24 hour rhythm of clock-core and clock-controlled gene expression indicated that nicotinamide phosphoribosyltransferase (Nampt) was the most sensitive gene to GSPE. However, Nampt was repressed or overexpressed after GSPE administration at ZT0 or ZT12, respectively. NAD levels, which are controlled by Nampt and also exhibit circadian rhythm, decreased or increased according to Nampt expression. Moreover, the ratio of acetylated Bmal1, that directly drives Nampt expression, only increased when GSPE was administered at ZT12. Therefore, GSPE modulated the clock system in the liver, suggesting that PAs can regulate lipid and glucose metabolism by adjusting the circadian rhythm in the liver.
authors.affiliation: Nutrigenomic Research Group. Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Aleix
authors.initials: A
authors.lastname: Ribas-Latre
authors.affiliation: Nutrigenomic Research Group. Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Baselga-Escudero
authors.affiliation: Nutrigenomic Research Group. Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Casanova
authors.affiliation: Nutrigenomic Research Group. Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Arola-Arnal
authors.affiliation: Nutrigenomic Research Group. Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: M-Josepa
authors.initials: MJ
authors.lastname: Salvadó
authors.affiliation: Nutrigenomic Research Group. Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Cinta
authors.initials: C
authors.lastname: Bladé
authors.affiliation: Nutrigenomic Research Group. Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Lluís
authors.initials: L
authors.lastname: Arola
mesh_terms: D056930:ARNTL Transcription Factors / Q000378:metabolism*; D000107:Acetylation / Q000187:drug effects; D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D009243:NAD / Q000378:metabolism*; D054409:Nicotinamide Phosphoribosyltransferase / Q000096:biosynthesis*; D044945:Proanthocyanidins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D056930:ARNTL Transcription Factors; C000598703:Arntl protein, rat; D016207:Cytokines; D044945:Proanthocyanidins; D009243:NAD; C013221:proanthocyanidin; D054409:Nicotinamide Phosphoribosyltransferase; C504970:nicotinamide phosphoribosyltransferase, rat; D005947:Glucose