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

Genes
Laura Liñares-PoseMiguel López

Abstract

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.

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Citations

Jul 23, 2019·Journal of Neuroendocrinology·Pamela R HirschbergVanessa H Routh
Jan 11, 2020·Frontiers in Endocrinology·Edward Milbank, Miguel López
May 30, 2019·Genes·Benoit R Gauthier, Francisco J Bermúdez-Silva
Dec 18, 2019·Journal of Physiology and Biochemistry·Ismael González-GarcíaCristina Contreras
Oct 20, 2020·Frontiers in Endocrinology·Hailan LiuFang Hu
Sep 29, 2020·Pharmacology & Therapeutics·Patricia Seoane-CollazoMiguel López
Jun 4, 2021·Toxicology and Applied Pharmacology·Rada CherngwellingAnusorn Lungkaphin

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Methods Mentioned

BETA
PCR
protein folding

Software Mentioned

ImageJ
FLIR
- Tools

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