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Article

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

1
Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria de Santiago de Compostela, 15782 Santiago de Compostela, Spain
2
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706 Santiago de Compostela, Spain
3
Department of Physiology, School of Pharmacy, Universidad Complutense de Madrid, 28040 Madrid, Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Genes 2018, 9(7), 357; https://doi.org/10.3390/genes9070357
Received: 16 June 2018 / Revised: 7 July 2018 / Accepted: 10 July 2018 / Published: 17 July 2018
(This article belongs to the Special Issue Advances in Genetics of Regeneration in Metabesity)
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. View Full-Text
Keywords: brown adipose tissue; browning; ER stress; GRP78; hypothalamus; thermogenesis; white adipose tissue brown adipose tissue; browning; ER stress; GRP78; hypothalamus; thermogenesis; white adipose tissue
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MDPI and ACS Style

Liñares-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, 357. https://doi.org/10.3390/genes9070357

AMA Style

Liñares-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(7):357. https://doi.org/10.3390/genes9070357

Chicago/Turabian Style

Liñares-Pose, Laura, 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, and Miguel López. 2018. "Genetic Targeting of GRP78 in the VMH Improves Obesity Independently of Food Intake" Genes 9, no. 7: 357. https://doi.org/10.3390/genes9070357

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