Hypothalamic GRP78, a new target against obesity?

Cristina Contreras; Marcos F Fondevila; Miguel López

doi:10.1080/21623945.2017.1405878

Hypothalamic GRP78, a new target against obesity?

Adipocyte. 2018 Jan 2;7(1):63-66. doi: 10.1080/21623945.2017.1405878. Epub 2017 Dec 20.

Authors

Cristina Contreras^{1

2}, Marcos F Fondevila^{1

2}, Miguel López^{1

2}

Affiliations

¹ a NeurObesity Group, Department of Physiology, CIMUS , University of Santiago de Compostela, -Instituto de Investigación Sanitaria , Santiago de Compostela , Spain.
² b CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn) , Santiago de Compostela , Spain.

Abstract

The chaperone GRP78 (glucose related protein 78), also called BiP (binding immunoglobulin protein) is a key regulator of endoplasmic reticulum (ER) stress. We recently described that over-expression of GRP78 specifically in the ventromedial nucleus of the hypothalamus (VMH) releases hypothalamic ER stress in rodent obese models leading to weight loss, reduced hepatic steatosis and improved insulin and leptin sensitivity. The action of GRP78 is mediated by a feeding-independent mechanism involving increased sympathetic tone, augmented brown adipose tissue (BAT) thermogenesis and induction browning of white adipose tissue (WAT).

Keywords: BAT; ER stress; GRP78; browning; hypothalamus; obesity; thermogenesis.

Publication types

Review

MeSH terms

Adipose Tissue, Brown / metabolism
Animals
Endoplasmic Reticulum Chaperone BiP
Endoplasmic Reticulum Stress / genetics
Endoplasmic Reticulum Stress / physiology
Heat-Shock Proteins / genetics
Heat-Shock Proteins / metabolism*
Humans
Hypothalamus / metabolism*
Obesity / metabolism*
Thermogenesis / genetics
Thermogenesis / physiology

Substances

Endoplasmic Reticulum Chaperone BiP
HSPA5 protein, human
Heat-Shock Proteins

Grants and funding

Xunta de Galicia (2015–CP079), Ministry of Economy and Competitiveness (SAF2015–71026–R) and AtresMedia. CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of ISCIII. The funders had no role in decision to publish, or preparation of the manuscript.