title: Intake of grape procyanidins during gestation and lactation impairs reverse cholesterol transport and increases atherogenic risk indexes in adult offspring.
abstract: Cardiovascular disease (CVD) is one of the most prevalent noncommunicable diseases in humans. Different studies have identified dietary procyanidins as bioactive compounds with beneficial properties against CVD by improving lipid homeostasis, among other mechanisms. The aim of this work was to assess whether grape seed procyanidin consumption at a physiological dose during the perinatal period could influence the CVD risk of the offspring. Wistar rat dams were treated with a grape seed procyanidin extract (GSPE; 25mg/kg of body weight per day) or vehicle during gestation and lactation. The adult male offspring of GSPE-treated dams presented decreased high-density lipoprotein cholesterol (HDL-C) levels, increased total cholesterol-to-HDL-C ratios and an exacerbated fasting triglyceride-to-HDL-C ratios (atherogenic index of plasma) compared to the control group. Impaired reverse cholesterol transport (RCT) was evidenced by the accumulation of cholesterol in skeletal muscle and by decreased fecal excretion of cholesterol and bile acids, which was consistent with the observed mRNA down-regulation of the rate-limiting enzyme in the hepatic bile acid synthesis pathway Cyp7A1. Conversely, GSPE programming also resulted in up-regulated gene expression of different key components of the RCT process, such as hepatic Npc1, Abcg1, Abca1, Lxra, Srebp2, Lcat, Scarb1 and Pltp, and the repression of microRNA miR-33a expression, a key negative controller of hepatic RCT at the gene expression level. Our results show that maternal intake of grape procyanidins during the perinatal period impacts different components of the RCT process, resulting in increased CVD risk in the adult offspring.
authors.affiliation: Grup de Recerca en Nutrició i Salut, Centre Tecnològic de Nutrició i Salut, TECNIO, CEICS, Reus, Spain. Electronic address: josep.delbas@ctns.cat.
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Del Bas
authors.affiliation: Grup de Recerca en Nutrició i Salut, Centre Tecnològic de Nutrició i Salut, TECNIO, CEICS, Reus, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Crescenti
authors.affiliation: Nutrigenomics Research Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Arola-Arnal
authors.affiliation: Department of Food Technology, University of Lleida, Lleida, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Oms-Oliu
authors.affiliation: Nutrigenomics Research Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Tarragona, Spain; Centre Tecnològic de Nutrició i Salut, TECNIO, CEICS, Reus, Spain.
authors.forename: Lluís
authors.initials: L
authors.lastname: Arola
authors.affiliation: Grup de Recerca en Nutrició i Salut, Centre Tecnològic de Nutrició i Salut, TECNIO, CEICS, Reus, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Caimari
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000737:chemistry; D002318:Cardiovascular Diseases / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000737:chemistry; D004032:Diet; D005243:Feces; D005260:Female; D056604:Grape Seed Extract; D006706:Homeostasis; D007774:Lactation / Q000502:physiology*; D008055:Lipids / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D059808:Polyphenols / Q000737:chemistry; D011247:Pregnancy; D011270:Pregnancy, Animal; D011297:Prenatal Exposure Delayed Effects; D044945:Proanthocyanidins / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D015854:Up-Regulation; D027843:Vitis / Q000737:chemistry*
chemical_list: D001647:Bile Acids and Salts; D008076:Cholesterol, HDL; D056604:Grape Seed Extract; D008055:Lipids; D059808:Polyphenols; D044945:Proanthocyanidins; D002784:Cholesterol
keywords: Cardiovascular disease; Grape seed procyanidins; Metabolic imprinting; Metabolic programming; Polyphenols; Reverse cholesterol transport; microRNA