title: The Addition of Liquid Fructose to a Western-Type Diet in LDL-R-/-Mice Induces Liver Inflammation and Fibrogenesis Markers without Disrupting Insulin Receptor Signalling after an Insulin Challenge.
abstract: A high consumption of fat and simple sugars, especially fructose, has been related to the development of insulin resistance, but the mechanisms involved in the effects of these nutrients are not fully understood. This study investigates the effects of a Western-type diet and liquid fructose supplementation, alone and combined, on insulin signalling and inflammation in low-density lipoprotein (LDL) receptor-deficient mice (LDL-R-/-). LDL-R-/-mice were fed chow or Western diet ±15% fructose solution for 12 weeks. Plasma glucose and insulin, and the expression of genes related to inflammation in the liver and visceral white adipose tissue (vWAT), were analysed. V-akt murine thymoma viral oncogene homolog-2 (Akt) activation was measured in the liver of the mice after a single injection of saline or insulin. None of the dietary interventions caused inflammation in vWAT, whereas the Western diet induced hepatic inflammation, which was further enhanced by liquid fructose, leading also to a significant increase in fibrogenesis markers. However, there was no change in plasma glucose or insulin, or insulin-induced Akt phosphorylation. In conclusion, hepatic inflammation and fibrogenesis markers induced by a Western diet supplemented with liquid fructose in LDL-R-/-mice are not associated with a significant impairment of hepatic insulin signalling.
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain. gemmasanguesa@gmail.com.|Institute of Biomedicine, University of Barcelona, 08028 Barcelona, Spain. gemmasanguesa@gmail.com.
authors.forename: Gemma
authors.initials: G
authors.lastname: Sangüesa
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain. miguelbiologo@gmail.com.|Institute of Biomedicine, University of Barcelona, 08028 Barcelona, Spain. miguelbiologo@gmail.com.
authors.forename: Miguel
authors.initials: M
authors.lastname: Baena
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain. nataliahutter@yahoo.es.
authors.forename: Natalia
authors.initials: N
authors.lastname: Hutter
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain. josemontanyesbq@gmail.com.
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Montañés
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain. rmsanchez@ub.edu.|Institute of Biomedicine, University of Barcelona, 08028 Barcelona, Spain. rmsanchez@ub.edu.|CIBER Fisiología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Spain. rmsanchez@ub.edu.
authors.forename: Rosa María
authors.initials: RM
authors.lastname: Sánchez
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain. roglans@ub.edu.|Institute of Biomedicine, University of Barcelona, 08028 Barcelona, Spain. roglans@ub.edu.|CIBER Fisiología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Spain. roglans@ub.edu.
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, 08028 Barcelona, Spain. jclagunae@ub.edu.|Institute of Biomedicine, University of Barcelona, 08028 Barcelona, Spain. jclagunae@ub.edu.|CIBER Fisiología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Spain. jclagunae@ub.edu.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Laguna
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain. alegret@ub.edu.|Institute of Biomedicine, University of Barcelona, 08028 Barcelona, Spain. alegret@ub.edu.|CIBER Fisiología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Spain. alegret@ub.edu.
authors.forename: Marta
authors.initials: M
authors.lastname: Alegret
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D052436:Adipose Tissue, White / Q000503:physiopathology; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D066273:Diet, Western / Q000009:adverse effects*; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects*; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D008099:Liver / Q000503:physiopathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism; D015398:Signal Transduction; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D000410:Alanine Transaminase; D015415:Biomarkers; D001786:Blood Glucose; D002352:Carrier Proteins; D005632:Fructose; D007328:Insulin; D008562:Membrane Glycoproteins; D011972:Receptor, Insulin; D011973:Receptors, LDL; D000099231:Lipopolysaccharide-Binding Protein
keywords: adipose tissue; high-fat diet; inflammasome; metabolism; simple sugars