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

Cell Reports. 2018;25(2):271-277.e4

 

Journal Homepage

Journal Title: Cell Reports

ISSN: 2211-1247 (Online)

Publisher: Elsevier

LCC Subject Category: Science: Biology (General)

Country of publisher: Netherlands

Language of fulltext: English

Full-text formats available: PDF, HTML

 

AUTHORS

Chaitanya K. Gavini (Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA)
Angie L. Bookout (Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA)
Raiza Bonomo (Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA)
Laurent Gautron (Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA)
Syann Lee (Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA)
Virginie Mansuy-Aubert (Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA; Corresponding author)

EDITORIAL INFORMATION

Blind peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 31 weeks

 

Abstract | Full Text

Summary: 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: liver X receptors, DRG, neuropathy, ER stress, diet-induced obesity