title: Type of supplemented simple sugar, not merely calorie intake, determines adverse effects on metabolism and aortic function in female rats.
abstract: High consumption of simple sugars causes adverse cardiometabolic effects. We investigated the mechanisms underlying the metabolic and vascular effects of glucose or fructose intake and determined whether these effects are exclusively related to increased calorie consumption. Female Sprague-Dawley rats were supplemented with 20% wt/vol glucose or fructose for 2 mo, and plasma analytes and aortic response to vasodilator and vasoconstrictor agents were determined. Expression of molecules associated with lipid metabolism, insulin signaling, and vascular response were evaluated in hepatic and/or aortic tissues. Caloric intake was increased in both sugar-supplemented groups vs. control and in glucose- vs. fructose-supplemented rats. Hepatic lipogenesis was induced in both groups. Plasma triglycerides were increased only in the fructose group, together with decreased expression of carnitine palmitoyltransferase-1A and increased microsomal triglyceride transfer protein expression in the liver. Plasma adiponectin and peroxisome proliferator-activated receptor (PPAR)-α expression was increased only by glucose supplementation. Insulin signaling in liver and aorta was impaired in both sugar-supplemented groups, but the effect was more pronounced in the fructose group. Fructose supplementation attenuated aortic relaxation response to a nitric oxide (NO) donor, whereas glucose potentiated it. Phenylephrine-induced maximal contractions were reduced in the glucose group, which could be related to increased endothelial NO synthase (eNOS) phosphorylation and subsequent elevated basal NO in the glucose group. In conclusion, despite higher caloric intake in glucose-supplemented rats, fructose caused worse metabolic and vascular responses. This may be because of the elevated adiponectin level and the subsequent enhancement of PPARα and eNOS phosphorylation in glucose-supplemented rats.
  This is the first study comparing the effects of glucose and fructose consumption on metabolic factors and aortic function in female rats. Our results show that, although total caloric consumption was higher in glucose-supplemented rats, fructose ingestion had a greater impact in inducing metabolic and aortic dysfunction.
authors.affiliation: Department of Pharmacology, Toxicology, and Therapeutic Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Sangüesa
authors.affiliation: Department of Physiology & Pharmacology, Thomas J. Long School of Pharmacy & Health Sciences, University of the Pacific, Stockton, California.
authors.forename: Sonali
authors.initials: S
authors.lastname: Shaligram
authors.affiliation: Department of Physiology & Pharmacology, Thomas J. Long School of Pharmacy & Health Sciences, University of the Pacific, Stockton, California.
authors.forename: Farjana
authors.initials: F
authors.lastname: Akther
authors.affiliation: Department of Pharmacology, Toxicology, and Therapeutic Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.|Institute of Biomedicine, University of Barcelona, Barcelona, Spain; and.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Madrid, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Roglans
authors.affiliation: Department of Pharmacology, Toxicology, and Therapeutic Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.|Institute of Biomedicine, University of Barcelona, Barcelona, Spain; and.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Madrid, Spain.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Laguna
authors.affiliation: Department of Physiology & Pharmacology, Thomas J. Long School of Pharmacy & Health Sciences, University of the Pacific, Stockton, California.
authors.forename: Roshanak
authors.initials: R
authors.lastname: Rahimian
authors.affiliation: Department of Pharmacology, Toxicology, and Therapeutic Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain; alegret@ub.edu.|Institute of Biomedicine, University of Barcelona, Barcelona, Spain; and.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Alegret
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D015153:Blotting, Western; D001920:Bradykinin / Q000494:pharmacology; D002334:Carnitine O-Palmitoyltransferase / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D019422:Dietary Sucrose / Q000494:pharmacology*; D002149:Energy Intake; D005260:Female; D005632:Fructose / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D050155:Lipogenesis / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D047493:PPAR alpha / Q000187:drug effects / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D014280:Triglycerides / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D052242:Adiponectin; C499920:Adipoq protein, rat; D002352:Carrier Proteins; D019422:Dietary Sucrose; D007328:Insulin; D020030:Nitric Oxide Donors; D047493:PPAR alpha; D014280:Triglycerides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C106092:microsomal triglyceride transfer protein; D009599:Nitroprusside; D010656:Phenylephrine; D005632:Fructose; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D002334:Carnitine O-Palmitoyltransferase; D005947:Glucose; D000109:Acetylcholine; D001920:Bradykinin
keywords: adiponectin; fructose; glucose; insulin resistance; liver