title: Limited beneficial effects of piceatannol supplementation on obesity complications in the obese Zucker rat: gut microbiota, metabolic, endocrine, and cardiac aspects.
abstract: Resveratrol is beneficial in obese and diabetic rodents. However, its low bioavailability raises questions about its therapeutic relevance for treating or preventing obesity complications. In this context, many related natural polyphenols are being tested for their putative antidiabetic and anti-obesity effects. This prompted us to study the influence of piceatannol, a polyhydroxylated stilbene, on the prevention of obesity complications in Zucker obese rats. A 6-week supplementation was followed by the determination of various markers in plasma, liver, adipose tissue and heart, together with a large-scale analysis of gut microbiota composition. When given in doses of 15 or 45 mg/kg body weight/day, piceatannol did not reduce either hyperphagia or fat accumulation. It did not modify the profusion of the most abundant phyla in gut, though slight changes were observed in the abundance of several Lactobacillus, Clostridium, and Bacteroides species belonging to Firmicutes and Bacteroidetes. This was accompanied by a tendency to reduce plasma lipopolysaccharides by 30 %, and by a decrease of circulating non-esterified fatty acids, LDL-cholesterol, and lactate. While piceatannol tended to improve lipid handling, it did not mitigate hyperinsulinemia and cardiac hypertrophy. However, it increased cardiac expression of ephrin-B1, a membrane protein that contributes to maintaining cardiomyocyte architecture. Lastly, ascorbyl radical plasma levels and hydrogen peroxide release by adipose tissue were similar in control and treated groups. Thus, piceatannol did not exhibit strong slimming capacities but did limit several obesity complications.
authors.affiliation: Department of Gastroenterology, Biodonostia Research Institute, University of Basque Country (UPV/EHU), San Sebastián, Spain.|Centro de Investigación Biomédica en Enfermedades Hepáticas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Hijona
authors.affiliation: Nutrition and Obesity Group, Department of Nutrition and Food Science, University of Basque Country (UPV/EHU), Vitoria, Spain. leixuri.aguirre@ehu.eus.|CIBER Fisiopatología Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain. leixuri.aguirre@ehu.eus.
authors.forename: L
authors.initials: L
authors.lastname: Aguirre
authors.affiliation: HIV and Associated Metabolic Alterations Unit, Infectious Diseases Department, Center for Biomedical Research of La Rioja (CIBIR), Logroño, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Pérez-Matute
authors.affiliation: HIV and Associated Metabolic Alterations Unit, Infectious Diseases Department, Center for Biomedical Research of La Rioja (CIBIR), Logroño, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Villanueva-Millán
authors.affiliation: Nutrition and Obesity Group, Department of Nutrition and Food Science, University of Basque Country (UPV/EHU), Vitoria, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Mosqueda-Solis
authors.affiliation: INSERM U1048, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, France.
authors.forename: M
authors.initials: M
authors.lastname: Hasnaoui
authors.affiliation: University of Toulouse, UPS and IRD, UMR 152 (PHARMA-DEV), F-31062, Toulouse cedex 9, France.
authors.forename: F
authors.initials: F
authors.lastname: Nepveu
authors.affiliation: INSERM U1048, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Senard
authors.affiliation: Department of Gastroenterology, Biodonostia Research Institute, University of Basque Country (UPV/EHU), San Sebastián, Spain.|Centro de Investigación Biomédica en Enfermedades Hepáticas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Bujanda
authors.affiliation: Division of Metabolism, Cruces University Hospital and BioCruces Health Research Institute, Plaza de Cruces s/n, 48903, Barakaldo, Spain.|GCV-CIBER de Enfermedades Raras (CIBERer), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Aldámiz-Echevarría
authors.affiliation: Division of Metabolism, Cruces University Hospital and BioCruces Health Research Institute, Plaza de Cruces s/n, 48903, Barakaldo, Spain.|GCV-CIBER de Enfermedades Raras (CIBERer), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Llarena
authors.affiliation: Division of Metabolism, Cruces University Hospital and BioCruces Health Research Institute, Plaza de Cruces s/n, 48903, Barakaldo, Spain.|GCV-CIBER de Enfermedades Raras (CIBERer), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Andrade
authors.affiliation: University of Toulouse, UPS and IRD, UMR 152 (PHARMA-DEV), F-31062, Toulouse cedex 9, France.
authors.forename: P
authors.initials: P
authors.lastname: Perio
authors.affiliation: INSERM U1048, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, France.
authors.forename: F
authors.initials: F
authors.lastname: Leboulanger
authors.affiliation: Department of Gastroenterology, Biodonostia Research Institute, University of Basque Country (UPV/EHU), San Sebastián, Spain.|Centro de Investigación Biomédica en Enfermedades Hepáticas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Hijona
authors.affiliation: CIBER Fisiopatología Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.|Adipocyte and Fat Biology Laboratory (AdipoFat), Unidad de Investigación Traslacional, Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Arbones-Mainar
authors.affiliation: Nutrition and Obesity Group, Department of Nutrition and Food Science, University of Basque Country (UPV/EHU), Vitoria, Spain.|CIBER Fisiopatología Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: M P
authors.initials: MP
authors.lastname: Portillo
authors.affiliation: INSERM U1048, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, France.
authors.forename: C
authors.initials: C
authors.lastname: Carpéné
mesh_terms: D041721:3T3-L1 Cells; D052436:Adipose Tissue, White / Q000276:immunology / Q000378:metabolism; D050154:Adiposity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D019587:Dietary Supplements; D064806:Dysbiosis / Q000209:etiology / Q000517:prevention & control*; D006331:Heart Diseases / Q000209:etiology / Q000517:prevention & control*; D006861:Hydrogen Peroxide / Q000378:metabolism; D006949:Hyperlipidemias / Q000209:etiology / Q000517:prevention & control; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D009206:Myocardium / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000178:diet therapy* / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology; D011897:Random Allocation; D011924:Rats, Zucker; D013267:Stilbenes / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D015415:Biomarkers; D013267:Stilbenes; C041525:3,3',4,5'-tetrahydroxystilbene; D006861:Hydrogen Peroxide
keywords: Adipokines; Adipose tissue; Cardiomyocytes; Gut microbiota; Liver; Piceatannol; Zucker rat