Genes, Vol. 9, Pages 357: Genetic Targeting of GRP78 in the VMH Improves Obesity Independently of Food Intake

Genes, Vol. 9, Pages 357: Genetic Targeting of GRP78 in the VMH Improves Obesity Independently of Food Intake Genes doi: 10.3390/genes9070357 Authors: Laura Liñares-Pose Eva Rial-Pensado Ánxela Estévez-Salguero Edward Milbank Ismael González-García Claudia Rodríguez Patricia Seoane-Collazo Noelia Martinez-Sánchez Rubén Nogueiras Dolores Prieto Carlos Diéguez Cristina Contreras Miguel López Recent 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 obesity.
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Article Source Type: research