Liver X Receptors Protect Dorsal Root Ganglia from Obesity-Induced Endoplasmic Reticulum Stress and Mechanical Allodynia

Chaitanya K. Gavini, Angie L. Bookout, Raiza Bonomo, Laurent Gautron, Syann Lee, Virginie Mansuy-Aubert

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Obesity is associated with many complications, including type 2 diabetes and painful neuropathy. There is no cure or prevention for obesity-induced pain, and the neurobiology underlying the onset of the disease is still obscure. In this study, we observe that western diet (WD)-fed mice developed early allodynia with an increase of ER stress markers in the sensory neurons of the dorsal root ganglia (DRG). Using cell-specific approaches, we demonstrate that neuronal liver X receptor (LXR) activation delays ER stress and allodynia in WD-fed mice. Our findings suggest that lipid-binding nuclear receptors expressed in the sensory neurons of the DRG play a role in the onset of obesity-induced hypersensitivity. The LXR and lipid-sensor pathways represent a research avenue to identify targets to prevent debilitating complications affecting the peripheral nerve system in obesity. The mechanism underlying obesity-induced pain is explored by Gavini et al. using cell-specific models. Their analysis reveals that in sensory neurons of the dorsal root ganglia, LXR activation delays western diet-induced ER stress and allodynia. These findings suggest that LXRs in sensory neurons are involved in nociception induced by western diet nutrition.

Original languageEnglish (US)
Pages (from-to)271-277.e4
JournalCell Reports
Volume25
Issue number2
DOIs
StatePublished - Oct 9 2018

Fingerprint

Endoplasmic Reticulum Stress
Hyperalgesia
Spinal Ganglia
Nutrition
Liver
Sensory Receptor Cells
Obesity
Neurons
Chemical activation
Lipids
Pain
Nociception
Neurobiology
Cytoplasmic and Nuclear Receptors
Medical problems
Peripheral Nerves
Type 2 Diabetes Mellitus
Hypersensitivity
Liver X Receptors
Western Diet

Keywords

  • diet-induced obesity
  • DRG
  • ER stress
  • liver X receptors
  • neuropathy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Liver X Receptors Protect Dorsal Root Ganglia from Obesity-Induced Endoplasmic Reticulum Stress and Mechanical Allodynia. / Gavini, Chaitanya K.; Bookout, Angie L.; Bonomo, Raiza; Gautron, Laurent; Lee, Syann; Mansuy-Aubert, Virginie.

In: Cell Reports, Vol. 25, No. 2, 09.10.2018, p. 271-277.e4.

Research output: Contribution to journalArticle

@article{7903e0ac6c35486495da231ffe5de971,
title = "Liver X Receptors Protect Dorsal Root Ganglia from Obesity-Induced Endoplasmic Reticulum Stress and Mechanical Allodynia",
abstract = "Obesity is associated with many complications, including type 2 diabetes and painful neuropathy. There is no cure or prevention for obesity-induced pain, and the neurobiology underlying the onset of the disease is still obscure. In this study, we observe that western diet (WD)-fed mice developed early allodynia with an increase of ER stress markers in the sensory neurons of the dorsal root ganglia (DRG). Using cell-specific approaches, we demonstrate that neuronal liver X receptor (LXR) activation delays ER stress and allodynia in WD-fed mice. Our findings suggest that lipid-binding nuclear receptors expressed in the sensory neurons of the DRG play a role in the onset of obesity-induced hypersensitivity. The LXR and lipid-sensor pathways represent a research avenue to identify targets to prevent debilitating complications affecting the peripheral nerve system in obesity. The mechanism underlying obesity-induced pain is explored by Gavini et al. using cell-specific models. Their analysis reveals that in sensory neurons of the dorsal root ganglia, LXR activation delays western diet-induced ER stress and allodynia. These findings suggest that LXRs in sensory neurons are involved in nociception induced by western diet nutrition.",
keywords = "diet-induced obesity, DRG, ER stress, liver X receptors, neuropathy",
author = "Gavini, {Chaitanya K.} and Bookout, {Angie L.} and Raiza Bonomo and Laurent Gautron and Syann Lee and Virginie Mansuy-Aubert",
year = "2018",
month = "10",
day = "9",
doi = "10.1016/j.celrep.2018.09.046",
language = "English (US)",
volume = "25",
pages = "271--277.e4",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - Liver X Receptors Protect Dorsal Root Ganglia from Obesity-Induced Endoplasmic Reticulum Stress and Mechanical Allodynia

AU - Gavini, Chaitanya K.

AU - Bookout, Angie L.

AU - Bonomo, Raiza

AU - Gautron, Laurent

AU - Lee, Syann

AU - Mansuy-Aubert, Virginie

PY - 2018/10/9

Y1 - 2018/10/9

N2 - Obesity is associated with many complications, including type 2 diabetes and painful neuropathy. There is no cure or prevention for obesity-induced pain, and the neurobiology underlying the onset of the disease is still obscure. In this study, we observe that western diet (WD)-fed mice developed early allodynia with an increase of ER stress markers in the sensory neurons of the dorsal root ganglia (DRG). Using cell-specific approaches, we demonstrate that neuronal liver X receptor (LXR) activation delays ER stress and allodynia in WD-fed mice. Our findings suggest that lipid-binding nuclear receptors expressed in the sensory neurons of the DRG play a role in the onset of obesity-induced hypersensitivity. The LXR and lipid-sensor pathways represent a research avenue to identify targets to prevent debilitating complications affecting the peripheral nerve system in obesity. The mechanism underlying obesity-induced pain is explored by Gavini et al. using cell-specific models. Their analysis reveals that in sensory neurons of the dorsal root ganglia, LXR activation delays western diet-induced ER stress and allodynia. These findings suggest that LXRs in sensory neurons are involved in nociception induced by western diet nutrition.

AB - Obesity is associated with many complications, including type 2 diabetes and painful neuropathy. There is no cure or prevention for obesity-induced pain, and the neurobiology underlying the onset of the disease is still obscure. In this study, we observe that western diet (WD)-fed mice developed early allodynia with an increase of ER stress markers in the sensory neurons of the dorsal root ganglia (DRG). Using cell-specific approaches, we demonstrate that neuronal liver X receptor (LXR) activation delays ER stress and allodynia in WD-fed mice. Our findings suggest that lipid-binding nuclear receptors expressed in the sensory neurons of the DRG play a role in the onset of obesity-induced hypersensitivity. The LXR and lipid-sensor pathways represent a research avenue to identify targets to prevent debilitating complications affecting the peripheral nerve system in obesity. The mechanism underlying obesity-induced pain is explored by Gavini et al. using cell-specific models. Their analysis reveals that in sensory neurons of the dorsal root ganglia, LXR activation delays western diet-induced ER stress and allodynia. These findings suggest that LXRs in sensory neurons are involved in nociception induced by western diet nutrition.

KW - diet-induced obesity

KW - DRG

KW - ER stress

KW - liver X receptors

KW - neuropathy

UR - http://www.scopus.com/inward/record.url?scp=85054126056&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054126056&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2018.09.046

DO - 10.1016/j.celrep.2018.09.046

M3 - Article

C2 - 30304667

AN - SCOPUS:85054126056

VL - 25

SP - 271-277.e4

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 2

ER -