Liñares Pose, LauraRial Pensado, EvaEstévez Salguero, ÁnxelaMilbank, EdwardGonzález García, IsmaelRodríguez, ClaudiaSeoane Collazo, PatriciaMartínez Sánchez, NoeliaNogueiras Pozo, RubénPrieto, DoloresDiéguez González, CarlosContreras, CristinaLópez Pérez, Miguel A.2020-05-062020-05-062018Liñares-Pose, L.; Rial-Pensado, E.; Estévez-Salguero, Á.; Milbank, E.; González-García, I.; Rodríguez, C.; Seoane-Collazo, P.; Martinez-Sánchez, N.; Nogueiras, R.; Prieto, D.; Diéguez, C.; Contreras, C.; López, M. Genetic Targeting of GRP78 in the VMH Improves Obesity Independently of Food Intake. Genes 2018, 9, 357http://hdl.handle.net/10347/22089Recent data have demonstrated that the hypothalamic GRP78/BiP (glucose regulated protein 78 kDa/binding immunoglobulin protein) modulates brown adipose tissue (BAT) thermogenesis by acting downstream on AMP-activated protein kinase (AMPK). Herein, we aimed to investigate whether genetic over-expression of GRP78 in the ventromedial nucleus of the hypothalamus (VMH: a key site regulating thermogenesis) could ameliorate very high fat diet (vHFD)-induced obesity. Our data showed that stereotaxic treatment with adenoviruses harboring GRP78 in the VMH reduced hypothalamic endoplasmic reticulum ER stress and reversed vHFD-induced obesity. Herein, we also demonstrated that this body weight decrease was more likely associated with an increased BAT thermogenesis and browning of white adipose tissue (WAT) than to anorexia. Overall, these results indicate that the modulation of GRP78 in the VMH may be a target against obesityeng© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)https://creativecommons.org/licenses/by/4.0/Brown adipose tissueBrowningER stressGRP78HypothalamusThermogenesisWhite adipose tissuestressGRP78HypothalamusThermogenesisWhite adipose tissuejournal article10.3390/genes90703572073-4425open access