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Title: Reduction of Hypothalamic Endoplasmic Reticulum Stress Activates Browning of White Fat and Ameliorates Obesity.
Authors: Contreras, Cristina
González-García, Ismael
Seoane-Collazo, Patricia
Martínez-Sánchez, Noelia
Liñares-Pose, Laura
Rial-Pensado, Eva
Fernø, Johan
Tena-Sempere, Manuel
Casals, Núria
Diéguez, Carlos
Nogueiras, Rubén
López, Miguel
metadata.dc.subject.mesh: Adipose Tissue, Brown
Adipose Tissue, White
Blotting, Western
Diet, High-Fat
Endoplasmic Reticulum Stress
Fatty Acids, Nonesterified
Rats, Sprague-Dawley
Real-Time Polymerase Chain Reaction
Taurochenodeoxycholic Acid
Issue Date: 15-Sep-2016
Abstract: The chaperone GRP78/BiP (glucose-regulated protein 78 kDa/binding immunoglobulin protein) modulates protein folding in reply to cellular insults that lead to endoplasmic reticulum (ER) stress. This study investigated the role of hypothalamic GRP78 on energy balance, with particular interest in thermogenesis and browning of white adipose tissue (WAT). For this purpose, we used diet-induced obese rats and rats administered thapsigargin, and by combining metabolic, histologic, physiologic, pharmacologic, thermographic, and molecular techniques, we studied the effect of genetic manipulation of hypothalamic GRP78. Our data showed that rats fed a high-fat diet or that were centrally administered thapsigargin displayed hypothalamic ER stress, whereas genetic overexpression of GRP78 specifically in the ventromedial nucleus of the hypothalamus was sufficient to alleviate ER stress and to revert the obese and metabolic phenotype. Those effects were independent of feeding and leptin but were related to increased thermogenic activation of brown adipose tissue and induction of browning in WAT and could be reversed by antagonism of β3 adrenergic receptors. This evidence indicates that modulation of hypothalamic GRP78 activity may be a potential strategy against obesity and associated comorbidities.
metadata.dc.identifier.doi: 10.2337/db15-1547
Appears in Collections:Producción 2020

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