title: Chronic consumption of dietary proanthocyanidins modulates peripheral clocks in healthy and obese rats.
abstract: Circadian rhythm plays an important role in maintaining homeostasis, and its disruption increases the risk of developing metabolic syndrome. Circadian rhythm is maintained by a central clock in the hypothalamus that is entrained by light, but circadian clocks are also present in peripheral tissues. These peripheral clocks are trained by other cues, such as diet. The aim of this study was to determine whether proanthocyanidins, the most abundant polyphenols in the human diet, modulate the expression of clock and clock-controlled genes in the liver, gut and mesenteric white adipose tissue (mWAT) in healthy and obese rats. Grape seed proanthocyanidin extracts (GSPEs) were administered for 21 days at 5, 25 or 50 mg GSPE/kg body weight in healthy rats and 25 mg GSPE/kg body weight in rats with diet-induced obesity. In healthy animals, GSPE administration led to the overexpression of core clock genes in a positive dose-dependent manner. Moreover, the acetylated BMAL1 protein ratio increased with the same pattern in the liver and mWAT. With regards to clock-controlled genes, Per2 was also overexpressed, whereas Rev-erbα and RORα were repressed in a negative dose-dependent manner. Diet-induced obesity always resulted in the overexpression of some core clock and clock-related genes, although the particular gene affected was tissue specific. GSPE administration counteracted disturbances in the clock genes in the liver and gut but was less effective in normalizing the clock gene disruption in WAT. In conclusion, proanthocyanidins have the capacity to modulate peripheral molecular clocks in both healthy and obese states.
authors.affiliation: Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Ribas-Latre
authors.affiliation: Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Baselga-Escudero
authors.affiliation: Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Casanova
authors.affiliation: Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Arola-Arnal
authors.affiliation: Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Salvadó
authors.affiliation: Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, Spain. Electronic address: lluis.arola@urv.cat.
authors.forename: L
authors.initials: L
authors.lastname: Arola
authors.affiliation: Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Bladé
mesh_terms: D056930:ARNTL Transcription Factors / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D000818:Animals; D021081:Chronobiology Disorders / Q000209:etiology / Q000517:prevention & control*; D019587:Dietary Supplements; D004386:Duodenum / Q000378:metabolism; D005786:Gene Expression Regulation; D056604:Grape Seed Extract / Q000008:administration & dosage / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000209:etiology / Q000517:prevention & control; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000178:diet therapy* / Q000378:metabolism / Q000503:physiopathology; D009928:Organ Specificity; D056950:Period Circadian Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000209:etiology / Q000517:prevention & control*; D044945:Proanthocyanidins / Q000008:administration & dosage / Q000627:therapeutic use*; D011897:Random Allocation; D017208:Rats, Wistar
chemical_list: D056930:ARNTL Transcription Factors; C000598703:Arntl protein, rat; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D000960:Hypolipidemic Agents; C498263:Nr1d1 protein, rat; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C513311:Per2 protein, rat; D056950:Period Circadian Proteins; D044945:Proanthocyanidins; C000598704:Roralpha protein, rat
keywords: Bmal1; Clock; Flavonoids; Per2; RORα; Rev-erbα