Impact of liver-specific GLUT8 silencing on fructose-induced inflammation and omega oxidation

Marta G Novelle; Susana Belén Bravo; Maxime Deshons; Cristina Iglesias; María García-Vence; Rebecca Annells; Natália da Silva Lima; Rubén Nogueiras; Manuel Alejandro Fernández-Rojo; Carlos Diéguez; Amparo Romero-Picó

doi:10.1016/j.isci.2021.102071

Impact of liver-specific GLUT8 silencing on fructose-induced inflammation and omega oxidation

iScience. 2021 Jan 19;24(2):102071. doi: 10.1016/j.isci.2021.102071. eCollection 2021 Feb 19.

Affiliations

¹ Functional Obeosomics and Molecular Metabolism laboratories, Centro singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CiMUS), Universidad de Santiago de Compostela, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Av. Barcelona s/n 15782, A Coruña, Santiago de Compostela, Spain.
² Hepatic Regenerative Medicine Laboratory, Madrid Institute for Advanced Studies (IMDEA) in Food, CEI UAM+CSIC, Madrid, E28049, Spain.
³ Proteomic Unit, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain.
⁴ Laboratoire de Toxicologie, Faculté de Pharmacie, Université Clermont Auvergne, 63000, Clermont-Ferrand, France.
⁵ Department of Physiology, Anatomy and Genetics, University of Oxford, OX1 3PT, Oxford, UK.
⁶ School of Medicine, The University of Queensland, Herston, 4006, Brisbane, Australia.

Abstract

Excessive consumption of high-fructose diets is associated with insulin resistance, obesity, and non-alcoholic fatty liver disease (NAFLD). However, fructose differentially affects hepatic regulation of lipogenesis in males and females. Hence, additional studies are necessary in order to find strategies taking gender disparities in fructose-induced liver damage into consideration. Although the eighth member of facilitated glucose transporters (GLUT8) has been linked to fructose-induced macrosteatosis in female mice, its contribution to the inflammatory state of NAFLD remains to be elucidated. Combining pharmacological, biochemical, and proteomic approaches, we evaluated the preventive effect of targeted liver GLUT8 silencing on liver injury in a mice female fructose-induced non-alcoholic steatohepatitis female mouse model. Liver GLUT8-knockdown attenuated fructose-induced ER stress, recovered liver inflammation, and dramatically reduced fatty acid content, in part, via the omega oxidation. Therefore, this study links GLUT8 with liver inflammatory response and suggests GLUT8 as a potential target for the prevention of NAFLD.

Keywords: biological sciences; endocrinology; physiology.