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dc.creatorLopez-Pastor, A.R. (Andrea Raposo)-
dc.creatorGomez-Hernandez, A. (Almudena)-
dc.creatorDiaz-Castroverde, S. (Sabela)-
dc.creatorGonzález-Aseguinolaza, G. (Gloria)-
dc.creatorGonzalez-Rodriguez, A. (Agueda)-
dc.creatorCastillo-García, G. (Gema)-
dc.creatorFernandez, S. (Silvia)-
dc.creatorEscribano, O. (Oscar)-
dc.creatorBenito, M. (Manuel)-
dc.identifier.citationLopez-Pastor, A.R. (Andrea Raposo); Gomez-Hernandez, A. (Almudena); Diaz-Castroverde, S. (Sabela); et al. "Liver-specific insulin receptor isoform A expression enhances hepatic glucose uptake and ameliorates liver steatosis in a mouse model of diet-induced obesity". Disease Models & Mechanisms. 12 (2), 2019, dmm036186es
dc.description.abstractAmong the main complications associated with obesity are insulin resistance and altered glucose and lipid metabolism within the liver. It has previously been described that insulin receptor isoform A (IRA) favors glucose uptake and glycogen storage in hepatocytes compared with isoform B (IRB), improving glucose homeostasis in mice lacking liver insulin receptor. Thus, we hypothesized that IRA could also improve glucose and lipid metabolism in a mouse model of high-fatdiet-induced obesity. We addressed the role of insulin receptor isoforms in glucose and lipid metabolism in vivo. We expressed IRA or IRB specifically in the liver by using adeno-associated viruses (AAVs) in a mouse model of diet-induced insulin resistance and obesity. IRA, but not IRB, expression induced increased glucose uptake in the liver and muscle, improving insulin tolerance. Regarding lipid metabolism, we found that AAV-mediated IRA expression also ameliorated hepatic steatosis by decreasing the expression of Fasn, Pgc1a, Acaca and Dgat2 and increasing Scd-1 expression. Taken together, our results further unravel the role of insulin receptor isoforms in hepatic glucose and lipid metabolism in an insulin-resistant scenario. Our data strongly suggest that IRA is more efficient than IRB at favoring hepatic glucose uptake, improving insulin tolerance and ameliorating hepatic steatosis. Therefore, we conclude that a gene therapy approach for hepatic IRA expression could be a safe and promising tool for the regulation of hepatic glucose consumption and lipid metabolism, two key processes in the development of non-alcoholic fatty liver disease associated with obesity.es_ES
dc.description.sponsorshipThis work was supported by Ministerio de Ciencia e Innovación (SAF2011/22555, SAF2014/51795-R and SAF2017-82133-R to M.B.), Instituto de Salud Carlos III (PIE14/00061 and CB07/08/0001 to M.B.) and Comunidad de Madrid (CT1/18-CT2/ 18/PEJD-2017-PRE/BMD-4111 to A.R.L.-P.).es_ES
dc.publisherThe Company of Biologistses_ES
dc.subjectGlucose metabolismes_ES
dc.subjectInsulin receptor isoformses_ES
dc.subjectAdeno-associated viruseses_ES
dc.subjectGene therapyes_ES
dc.subjectNon-alcoholic fatty liver diseasees_ES
dc.subjectInsulin resistancees_ES
dc.titleLiver-specific insulin receptor isoform A expression enhances hepatic glucose uptake and ameliorates liver steatosis in a mouse model of diet-induced obesityes_ES
dc.description.noteThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.es_ES
dadun.citation.publicationNameDisease Models & Mechanismses_ES

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