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

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-express...

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Bibliographic Details
Published in:Genes 2018-07, Vol.9 (7), p.357
Main Authors: Liñares-Pose, Laura, Rial-Pensado, Eva, Estévez-Salguero, Ánxela, Milbank, Edward, González-García, Ismael, Rodríguez, Claudia, Seoane-Collazo, Patricia, Martinez-Sánchez, Noelia, Nogueiras, Rubén, Prieto, Dolores, Diéguez, Carlos, Contreras, Cristina, López, Miguel
Format: Article
Language:English
Subjects:
Adenoviruses
Adipose tissue
Adipose tissue (brown)
AMP
AMP-activated protein kinase
Animals
Anorexia
Body weight
Diabetes
Diet
Endoplasmic reticulum
Experiments
Food intake
Glucose
High fat diet
Hormones
Hypothalamus (ventromedial)
Insulin resistance
Liver
Obesity
Overexpression
Physiology
Proteins
Rodents
Software
Thermogenesis
Thyroid gland
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Summary: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.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes9070357