RT Journal Article
T1 Reduction of Hypothalamic Endoplasmic Reticulum Stress Activates Browning of White Fat and Ameliorates Obesity.
A1 Contreras, Cristina
A1 Gonzalez-Garcia, Ismael
A1 Seoane-Collazo, Patricia
A1 Martinez-Sanchez, Noelia
A1 Liñares-Pose, Laura
A1 Rial-Pensado, Eva
A1 Fernø, Johan
A1 Tena-Sempere, Manuel
A1 Casals, Nuria
A1 Dieguez, Carlos
A1 Nogueiras, Ruben
A1 Lopez, Miguel
K1 Adipose tissue, brown
K1 Adipose tissue, white
K1 Animals
K1 Blotting, Western
K1 Diet, high-fat
AB 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.
PB American Diabetes Association
YR 2016
FD 2016-09-09
LK http://hdl.handle.net/10668/10448
UL http://hdl.handle.net/10668/10448
LA en
NO Contreras C, González-García I, Seoane-Collazo P, Martínez-Sánchez N, Liñares-Pose L, Rial-Pensado E, et al. Reduction of Hypothalamic Endoplasmic Reticulum Stress Activates Browning of White Fat and Ameliorates Obesity. Diabetes. 2017 Jan;66(1):87-99
DS RISalud
RD Apr 12, 2025