Brain innate immunity regulates hypothalamic arcuate neuronal activity and feeding behavior

Wagner Luis Reis, Chun Xia Yi, Yuanqing Gao, Mathias H. Tschöp, Javier E. Stern

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Hypothalamic inflammation, involving microglia activation in the arcuate nucleus (ARC), is proposed as a novel underlying mechanism in obesity, insulin and leptin resistance. However, whether activated microglia affects ARC neuronal activity, and consequently basal and hormonal-induced food intake, is unknown. We show that lipopolysaccharide, an agonist of the toll-like receptor-4 (TLR4), which we found to be expressed in ARC microglia, inhibited the firing activity of the majority of orexigenic agouti gene-related protein/neuropeptide Y neurons, whereas it increased the activity of the majority of anorexigenic proopiomelanocortin neurons. Lipopolysaccharide effects in agouti gene-related protein/neuropeptide Y (but not in proopiomelanocortin) neurons were occluded by inhibiting microglia function or by blocking TLR4 receptors. Finally, we report that inhibition of hypothalamic microglia altered basal food intake, also preventing central orexigenic responses to ghrelin. Our studies support a major role for a TLR4-mediated microglia signaling pathway in the control of ARC neuronal activity and feeding behavior.

Original languageEnglish (US)
Pages (from-to)1303-1315
Number of pages13
JournalEndocrinology
Volume156
Issue number4
DOIs
StatePublished - Jan 1 2015

Fingerprint

Microglia
Feeding Behavior
Innate Immunity
Arcuate Nucleus of Hypothalamus
Toll-Like Receptor 4
Brain
Agouti-Related Protein
Pro-Opiomelanocortin
Neuropeptide Y
Neurons
Lipopolysaccharides
Eating
Ghrelin
Leptin
Insulin Resistance
Proteins
Obesity
Inflammation

ASJC Scopus subject areas

  • Endocrinology

Cite this

Reis, W. L., Yi, C. X., Gao, Y., Tschöp, M. H., & Stern, J. E. (2015). Brain innate immunity regulates hypothalamic arcuate neuronal activity and feeding behavior. Endocrinology, 156(4), 1303-1315. https://doi.org/10.1210/en.2014-1849

Brain innate immunity regulates hypothalamic arcuate neuronal activity and feeding behavior. / Reis, Wagner Luis; Yi, Chun Xia; Gao, Yuanqing; Tschöp, Mathias H.; Stern, Javier E.

In: Endocrinology, Vol. 156, No. 4, 01.01.2015, p. 1303-1315.

Research output: Contribution to journalArticle

Reis, WL, Yi, CX, Gao, Y, Tschöp, MH & Stern, JE 2015, 'Brain innate immunity regulates hypothalamic arcuate neuronal activity and feeding behavior', Endocrinology, vol. 156, no. 4, pp. 1303-1315. https://doi.org/10.1210/en.2014-1849
Reis, Wagner Luis ; Yi, Chun Xia ; Gao, Yuanqing ; Tschöp, Mathias H. ; Stern, Javier E. / Brain innate immunity regulates hypothalamic arcuate neuronal activity and feeding behavior. In: Endocrinology. 2015 ; Vol. 156, No. 4. pp. 1303-1315.
@article{494cf87975b64bcebdfac4f6737de4d6,
title = "Brain innate immunity regulates hypothalamic arcuate neuronal activity and feeding behavior",
abstract = "Hypothalamic inflammation, involving microglia activation in the arcuate nucleus (ARC), is proposed as a novel underlying mechanism in obesity, insulin and leptin resistance. However, whether activated microglia affects ARC neuronal activity, and consequently basal and hormonal-induced food intake, is unknown. We show that lipopolysaccharide, an agonist of the toll-like receptor-4 (TLR4), which we found to be expressed in ARC microglia, inhibited the firing activity of the majority of orexigenic agouti gene-related protein/neuropeptide Y neurons, whereas it increased the activity of the majority of anorexigenic proopiomelanocortin neurons. Lipopolysaccharide effects in agouti gene-related protein/neuropeptide Y (but not in proopiomelanocortin) neurons were occluded by inhibiting microglia function or by blocking TLR4 receptors. Finally, we report that inhibition of hypothalamic microglia altered basal food intake, also preventing central orexigenic responses to ghrelin. Our studies support a major role for a TLR4-mediated microglia signaling pathway in the control of ARC neuronal activity and feeding behavior.",
author = "Reis, {Wagner Luis} and Yi, {Chun Xia} and Yuanqing Gao and Tsch{\"o}p, {Mathias H.} and Stern, {Javier E.}",
year = "2015",
month = "1",
day = "1",
doi = "10.1210/en.2014-1849",
language = "English (US)",
volume = "156",
pages = "1303--1315",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "4",

}

TY - JOUR

T1 - Brain innate immunity regulates hypothalamic arcuate neuronal activity and feeding behavior

AU - Reis, Wagner Luis

AU - Yi, Chun Xia

AU - Gao, Yuanqing

AU - Tschöp, Mathias H.

AU - Stern, Javier E.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Hypothalamic inflammation, involving microglia activation in the arcuate nucleus (ARC), is proposed as a novel underlying mechanism in obesity, insulin and leptin resistance. However, whether activated microglia affects ARC neuronal activity, and consequently basal and hormonal-induced food intake, is unknown. We show that lipopolysaccharide, an agonist of the toll-like receptor-4 (TLR4), which we found to be expressed in ARC microglia, inhibited the firing activity of the majority of orexigenic agouti gene-related protein/neuropeptide Y neurons, whereas it increased the activity of the majority of anorexigenic proopiomelanocortin neurons. Lipopolysaccharide effects in agouti gene-related protein/neuropeptide Y (but not in proopiomelanocortin) neurons were occluded by inhibiting microglia function or by blocking TLR4 receptors. Finally, we report that inhibition of hypothalamic microglia altered basal food intake, also preventing central orexigenic responses to ghrelin. Our studies support a major role for a TLR4-mediated microglia signaling pathway in the control of ARC neuronal activity and feeding behavior.

AB - Hypothalamic inflammation, involving microglia activation in the arcuate nucleus (ARC), is proposed as a novel underlying mechanism in obesity, insulin and leptin resistance. However, whether activated microglia affects ARC neuronal activity, and consequently basal and hormonal-induced food intake, is unknown. We show that lipopolysaccharide, an agonist of the toll-like receptor-4 (TLR4), which we found to be expressed in ARC microglia, inhibited the firing activity of the majority of orexigenic agouti gene-related protein/neuropeptide Y neurons, whereas it increased the activity of the majority of anorexigenic proopiomelanocortin neurons. Lipopolysaccharide effects in agouti gene-related protein/neuropeptide Y (but not in proopiomelanocortin) neurons were occluded by inhibiting microglia function or by blocking TLR4 receptors. Finally, we report that inhibition of hypothalamic microglia altered basal food intake, also preventing central orexigenic responses to ghrelin. Our studies support a major role for a TLR4-mediated microglia signaling pathway in the control of ARC neuronal activity and feeding behavior.

UR - http://www.scopus.com/inward/record.url?scp=84926433834&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84926433834&partnerID=8YFLogxK

U2 - 10.1210/en.2014-1849

DO - 10.1210/en.2014-1849

M3 - Article

VL - 156

SP - 1303

EP - 1315

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 4

ER -