title: High-protein-low-carbohydrate diet: deleterious metabolic and cardiovascular effects depend on age.
abstract: High-protein-low-carbohydrate (HP-LC) diets have become widespread. Yet their deleterious consequences, especially on glucose metabolism and arteries, have already been underlined. Our previous study (2) has already shown glucose intolerance with major arterial dysfunction in very old mice subjected to an HP-LC diet. The hypothesis of this work was that this diet had an age-dependent deleterious metabolic and cardiovascular outcome. Two groups of mice, young and adult (3 and 6 mo old), were subjected for 12 wk to a standard or to an HP-LC diet. Glucose and lipid metabolism was studied. The cardiovascular system was explored from the functional stage with Doppler-echography to the molecular stage (arterial reactivity, mRNA, immunohistochemistry). Young mice did not exhibit any significant metabolic modification, whereas adult mice presented marked glucose intolerance associated with an increase in resistin and triglyceride levels. These metabolic disturbances were responsible for cardiovascular damages only in adult mice, with decreased aortic distensibility and left ventricle dysfunction. These seemed to be the consequence of arterial dysfunctions. Mesenteric arteries were the worst affected with a major oxidative stress, whereas aorta function seemed to be maintained with an appreciable role of cyclooxygenase-2 to preserve endothelial function. This study highlights for the first time the age-dependent deleterious effects of an HP-LC diet on metabolism, with glucose intolerance and lipid disorders and vascular (especially microvessels) and cardiac functions. This work shows that HP-LC lead to equivalent cardiovascular alterations, as observed in very old age, and underlines the danger of such diet.
authors.affiliation: Unite Mixte de Recherche-S 1140 Institut National de la Santé et de la Recherche Médicale, Faculty of Pharmacy, Paris Descartes University, Paris, France;
authors.forename: Tatiana
authors.initials: T
authors.lastname: Bedarida
authors.affiliation: Department of Physiology, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Unite Mixte de Recherche-S U970 Institut National de la Santé et de la Recherche Médicale, Faculty of Medicine, Paris Descartes University, Paris, France; stephanie.baron@egp.aphp.fr.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Baron
authors.affiliation: Centre National de la Recherche Scientifique Unite Mixte de Recherche 6214, Institut National de la Santé et de la Recherche Médicale U1083, Angers University, Angers, France;
authors.forename: Emilie
authors.initials: E
authors.lastname: Vessieres
authors.affiliation: Unite Mixte de Recherche-S 1139 Institut National de la Santé et de la Recherche Médicale, Faculty of Pharmacy, Paris Descartes University, Paris, France;
authors.forename: Francoise
authors.initials: F
authors.lastname: Vibert
authors.affiliation: Centre National de la Recherche Scientifique Unite Mixte de Recherche 6214, Institut National de la Santé et de la Recherche Médicale U1083, Angers University, Angers, France;
authors.forename: Audrey
authors.initials: A
authors.lastname: Ayer
authors.affiliation: Institut Cochin, Paris Descartes University, Paris, France;
authors.forename: Carmen
authors.initials: C
authors.lastname: Marchiol-Fournigault
authors.affiliation: Centre National de la Recherche Scientifique Unite Mixte de Recherche 6214, Institut National de la Santé et de la Recherche Médicale U1083, Angers University, Angers, France;
authors.forename: Daniel
authors.initials: D
authors.lastname: Henrion
authors.affiliation: Department of Biochemistry, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; EA 4529, Faculty of Pharmacy, Paris Sud University, Chatenay-Malabry, France;
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Paul
authors.affiliation: Institut National de la Santé et de la Recherche Médicale 705 Centre National de la Recherche Scientifique Unite Mixte de Recherche 8206, Faculty of Pharmacy, Paris Descartes University, Paris, France;
authors.forename: Florence
authors.initials: F
authors.lastname: Noble
authors.affiliation: ER4/EA 3974, Modeling in Clinical Research, Pierre and Marie Curie University, Paris, France;
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Golmard
authors.affiliation: Unite Mixte de Recherche-S 1139 Institut National de la Santé et de la Recherche Médicale, Faculty of Pharmacy, Paris Descartes University, Paris, France; Clinical Biochemistry, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France;
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Beaudeux
authors.affiliation: Unite Mixte de Recherche-S 1139 Institut National de la Santé et de la Recherche Médicale, Faculty of Pharmacy, Paris Descartes University, Paris, France; Unite Mixte de Recherche 1151 Institut National de la Santé et de la Recherche Médicale, Institut Necker-Enfants Malades, Paris Descartes University, Paris, France.
authors.forename: Charles-Henry
authors.initials: CH
authors.lastname: Cottart
authors.affiliation: Unite Mixte de Recherche-S 1140 Institut National de la Santé et de la Recherche Médicale, Faculty of Pharmacy, Paris Descartes University, Paris, France; Department of Biochemistry, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France;
authors.forename: Valerie
authors.initials: V
authors.lastname: Nivet-Antoine
mesh_terms: D000367:Age Factors; D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001786:Blood Glucose / Q000378:metabolism; D050528:Diet, Carbohydrate-Restricted / Q000009:adverse effects*; D004044:Dietary Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D004452:Echocardiography; D018149:Glucose Intolerance / Q000209:etiology* / Q000378:metabolism; D050356:Lipid Metabolism; D008638:Mesenteric Arteries / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D052243:Resistin / Q000097:blood; D014280:Triglycerides / Q000097:blood; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004044:Dietary Proteins; D052243:Resistin; D014280:Triglycerides
keywords: cardiovascular disease; glucose intolerance; high-protein-low-carbohydrate diet