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

11 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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