RT Journal Article
T1 Liver-specific insulin receptor isoform A expression enhances hepatic glucose uptake and ameliorates liver steatosis in a mouse model of diet-induced obesity
A1 Raposo López-Pastor, Andrea
A1 Gómez Hernández, María De La Almudena
A1 Díaz Castroverde, Sabela
A1 González-Aseguinolaza Gloria, 
A1 González Rodríguez, Águeda
A1 García, Gema
A1 Fernández, Silvia
A1 Escribano Illanes, Óscar
A1 Benito, Manuel
AB Among the main complications associated to obesity is insulin resistance and an altered glucose and lipid metabolism within the liver. It has been previously described that insulin receptor isoform A (IRA) favors glucose uptake and glycogen storage in hepatocytes as compared to 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 fat diet-induced obesity. We addressed the role of insulin receptor isoforms on glucose and lipid metabolism in vivo. We expressed IRA or IRB specifically in the liver by using adeno-associated viruses (AAV) in a mouse model of diet-induced insulin resistance and obesity. IRA expression, but not IRB, induced an 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. Taking 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 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 (NAFLD) associated to obesity.
SN 1754-8403
YR 2019
FD 2019
LK https://hdl.handle.net/20.500.14352/93392
UL https://hdl.handle.net/20.500.14352/93392
LA eng
NO Lopez-Pastor AR, Gomez-Hernandez A, Diaz-Castroverde S, Gonzalez-Aseguinolaza G, Gonzalez-Rodriguez A, Garcia G, 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 2019:dmm.036186. https://doi.org/10.1242/dmm.036186.
NO Ministerio de Ciencia e Innovación (España)
NO Instituto de Salud Carlos III
NO Comunidad de Madrid
DS Docta Complutense
RD 10 abr 2025