Miguel Baena1, Gemma Sangüesa1, Natalia Hutter2, José María Beltrán2, Rosa María Sánchez3, Núria Roglans3, Marta Alegret4, Juan Carlos Laguna5. 1. Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Science, University of Barcelona, Spain; Institute of Biomedicine University of Barcelona, Spain. 2. Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Science, University of Barcelona, Spain. 3. Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Science, University of Barcelona, Spain; Institute of Biomedicine University of Barcelona, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERObn), Spain. 4. Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Science, University of Barcelona, Spain; Institute of Biomedicine University of Barcelona, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERObn), Spain. Electronic address: alegret@ub.edu. 5. Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Science, University of Barcelona, Spain; Institute of Biomedicine University of Barcelona, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERObn), Spain. Electronic address: jclagunae@ub.edu.
Abstract
BACKGROUND/ OBJECTIVES: Liquid fructose associates with prevalence of type 2 diabetes mellitus and obesity. Intervention studies suggest that metabolically unfit individuals are more responsive than healthy individuals to liquid fructose. We determined whether mice consuming an obesogenic Western diet were more responsive than chow-fed mice to the alterations induced by liquid fructose supplementation (LFS). METHODS: C57BL/6N mice were fed chow or Western diet±ad libitum 15% fructose solution for 12 weeks. Food and liquid intake and body weight were monitored. Plasma analytes and liver lipids, histology and the expression of genes related to lipid handling, endoplasmic reticulum stress, inflammation and insulin signaling were analyzed. RESULTS: Western diet increased energy intake, visceral adipose tissue (vWAT), body weight, plasma and liver triglycerides and cholesterol, and inflammatory markers in vWAT vs. chow-fed mice. LFS did not change energy intake, vWAT or body weight. LFS significantly increased plasma and liver triglycerides and cholesterol levels only in Western-diet-fed mice. These changes associated with a potentiation of the increased liver expression of PPARγ and CD36 that was observed in Western-fed mice and related to the increased liver mTOR phosphorylation induced by LFS. Furthermore, LFS in Western-diet-fed mice induced the largest reduction in liver IRS2 protein and a significant decrease in whole-body insulin sensitivity. CONCLUSIONS: LFS in mice, in a background of an unhealthy diet that already induces fatty liver visceral fat accretion and obesity, increases liver lipid burden, hinders hepatic insulin signaling and diminishes whole-body insulin sensitivity without changing energy intake.
BACKGROUND/ OBJECTIVES: Liquid fructose associates with prevalence of type 2 diabetes mellitus and obesity. Intervention studies suggest that metabolically unfit individuals are more responsive than healthy individuals to liquid fructose. We determined whether mice consuming an obesogenic Western diet were more responsive than chow-fed mice to the alterations induced by liquid fructose supplementation (LFS). METHODS: C57BL/6N mice were fed chow or Western diet±ad libitum 15% fructose solution for 12 weeks. Food and liquid intake and body weight were monitored. Plasma analytes and liver lipids, histology and the expression of genes related to lipid handling, endoplasmic reticulum stress, inflammation and insulin signaling were analyzed. RESULTS: Western diet increased energy intake, visceral adipose tissue (vWAT), body weight, plasma and liver triglycerides and cholesterol, and inflammatory markers in vWAT vs. chow-fed mice. LFS did not change energy intake, vWAT or body weight. LFS significantly increased plasma and liver triglycerides and cholesterol levels only in Western-diet-fed mice. These changes associated with a potentiation of the increased liver expression of PPARγ and CD36 that was observed in Western-fed mice and related to the increased liver mTOR phosphorylation induced by LFS. Furthermore, LFS in Western-diet-fed mice induced the largest reduction in liver IRS2 protein and a significant decrease in whole-body insulin sensitivity. CONCLUSIONS: LFS in mice, in a background of an unhealthy diet that already induces fatty liver visceral fat accretion and obesity, increases liver lipid burden, hinders hepatic insulin signaling and diminishes whole-body insulin sensitivity without changing energy intake.
Authors: Gemma Sangüesa; Miguel Baena; Natalia Hutter; José Carlos Montañés; Rosa María Sánchez; Núria Roglans; Juan Carlos Laguna; Marta Alegret Journal: Nutrients Date: 2017-03-15 Impact factor: 5.717
Authors: Julia Beisner; Louisa Filipe Rosa; Valentina Kaden-Volynets; Iris Stolzer; Claudia Günther; Stephan C Bischoff Journal: Front Immunol Date: 2021-06-11 Impact factor: 7.561