Genetic Targeting of GRP78 in the VMH Improves Obesity Independently of Food Intake



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Liñares-Pose, Laura and Rial-Pensado, Eva and Estévez-Salguero, Ánxela and Milbank, Edward and González-García, Ismael and Rodríguez Prados, Claudia and Seoane-Collazo, Patricia and Martinez-Sánchez, Noelia and Nogueiras, Rubén and Prieto Ocejo, Dolores and Diéguez, Carlos and Contreras Jiménez, Cristina and López, Miguel (2018) Genetic Targeting of GRP78 in the VMH Improves Obesity Independently of Food Intake. Genes, 9 (7). p. 357. ISSN 2073-4425

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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.

Item Type:Article
Uncontrolled Keywords:brown adipose tissue; browning; ER stress; GRP78; hypothalamus; thermogenesis; white adipose tissue
Subjects:Medical sciences > Pharmacy > Pharmacology
ID Code:67109
Deposited On:26 Jul 2021 14:59
Last Modified:17 Aug 2021 08:19

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