LXR agonist modifies neuronal lipid homeostasis and decreases PGD2 in the dorsal root ganglia in western diet-fed mice

The prevalence of peripheral neuropathy is high in diabetic and overweight populations. Chronic neuropathic pain, a symptom of peripheral neuropathy, is a major disabling symptom that leads to a poor quality of life. Glucose management for diabetic and prediabetic individuals often fail to reduce or...

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Bibliographic Details
Published in:Scientific reports 2022-06, Vol.12 (1), p.10754-10754, Article 10754
Main Authors: Elshareif, Nadia, Gavini, Chaitanya K., Mansuy-Aubert, Virginie
Format: Article
Language:English
Subjects:
631/378/1959/2605
631/378/87
Agonists
Body weight
Cholesterol
Diabetes
Diabetes mellitus
Diabetic neuropathy
Diet
Dorsal root ganglia
Homeostasis
Humanities and Social Sciences
Lecithin
Lipids
Liver X receptors
Lysophosphatidylcholine
multidisciplinary
Nervous system
Neurosciences
Overweight
Pain
Pain perception
Peripheral neuropathy
Phosphatidylcholine
Phospholipids
Quality of life
Science
Science (multidisciplinary)
Sensory neurons
Transcription factors
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Summary:The prevalence of peripheral neuropathy is high in diabetic and overweight populations. Chronic neuropathic pain, a symptom of peripheral neuropathy, is a major disabling symptom that leads to a poor quality of life. Glucose management for diabetic and prediabetic individuals often fail to reduce or improve pain symptoms, therefore, exploring other mechanisms is necessary to identify effective treatments. A large body of evidence suggest that lipid signaling may be a viable target for management of peripheral neuropathy in obese individuals. The nuclear transcription factors, Liver X Receptors (LXR), are known regulators of lipid homeostasis, phospholipid remodeling, and inflammation. Notably, the activation of LXR using the synthetic agonist GW3965, delayed western diet (WD)-induced allodynia in rodents. To further understand the neurobiology underlying the effect of LXR, we used translating ribosome affinity purification and evaluated translatomic changes in the sensory neurons of WD-fed mice treated with the LXR agonist GW3965. We also observed that GW3965 decreased prostaglandin levels and decreased free fatty acid content, while increasing lysophosphatidylcholine, phosphatidylcholine, and cholesterol ester species in the sensory neurons of the dorsal root ganglia (DRG). These data suggest novel downstream interplaying mechanisms that modifies DRG neuronal lipid following GW3965 treatment.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-022-14604-0