title: Grape seed proanthocyanidin supplementation reduces adipocyte size and increases adipocyte number in obese rats.
abstract: White adipose tissue (WAT) expands through hypertrophy (increased adipocyte size) and/or hyperplasia (increased adipocyte number). Hypertrophy has been associated with insulin resistance and dyslipidemia independently of body composition and fat distribution. In contrast, hyperplasia protects against metabolic alterations. Proanthocyanidins, which are the most abundant flavonoids in the human diet, improve metabolic disturbances associated with diet-induced obesity without reducing body weight or adiposity. The aim of this study was to determine whether grape seed proanthocyanidin extract (GSPE) can modulate WAT expandability. Because GSPE also contains gallic acid, we also studied the capacity of gallic acid to remodel WAT.
  
  
  
  Male Wistar rats were fed a standard chow diet (n=6) or a cafeteria diet (CAF) for 11 weeks. After 8 weeks, the CAF-fed animals were supplemented with 25 mg GSPE/kg body weight (n=6), 7 mg gallic acid/kg body weight (n=6) or the vehicle (n=6) for 3 weeks. Histological analyses were performed in the retroperitoneal (rWAT) and inguinal (iWAT) WAT to determine adipocyte size and number. Specific markers for adipogenesis and WAT functionality were analysed in rWAT using quantitative RT-PCR.
  
  
  
  GSPE or gallic acid supplementation did not reduce weight gain or reverse and adiposity. However, GSPE reduced adipocyte size significantly in rWAT and moderately in iWAT and tripled the adipocyte number in rWAT. Gallic acid slightly reduced adipocyte size in rWAT and iWAT and doubled the adipocyte number in both WATs. In accordance with this adipogenic activity, Pref-1 and PPARγ tended to be overexpressed in rWAT of rats supplemented with GSPE. Moreover, GSPE supplementation increased Plin1 and Fabp4 expression and restored adiponectin expression completely, indicating a better functionality of visceral WAT.
  
  
  
  GSPE supplementation has anti-hypertrophic and hyperplasic activities in rats with established obesity, mainly in visceral WAT inducing a healthier expansion of WAT to match the surplus energy provided by the cafeteria diet.
authors.affiliation: Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili (URV), Tarragona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Pascual-Serrano
authors.affiliation: Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili (URV), Tarragona, Spain.
authors.forename: A
authors.identifier: 0000-0001-6529-1345
authors.initials: A
authors.lastname: Arola-Arnal
authors.affiliation: Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili (URV), Tarragona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Suárez-García
authors.affiliation: Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili (URV), Tarragona, Spain.
authors.forename: F I
authors.initials: FI
authors.lastname: Bravo
authors.affiliation: Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili (URV), Tarragona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Suárez
authors.affiliation: Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili (URV), Tarragona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Arola
authors.affiliation: Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili (URV), Tarragona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Bladé
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects* / Q000473:pathology; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004195:Disease Models, Animal; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005707:Gallic Acid / Q000494:pharmacology*; D005786:Gene Expression Regulation; D056604:Grape Seed Extract / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D009765:Obesity / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D000070778:Perilipin-1 / Q000378:metabolism; D044945:Proanthocyanidins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; C524662:FABP4 protein, rat; D050556:Fatty Acid-Binding Proteins; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D000070778:Perilipin-1; C000602981:Plin1 protein, rat; D044945:Proanthocyanidins; D005707:Gallic Acid