# Nuclear lipid-sensor in Type II Diabetic Neuropathy

> **NIH NIH R01** · LOYOLA UNIVERSITY CHICAGO · 2020 · $371,069

## Abstract

ABSTRACT
 Diabetic neuropathy is the most common complication of diabetes, affecting ~ 50% of obese individuals
with type II diabetes. Recent clinical and biological evidence indicate that painful type II diabetic neuropathy
is highly associated with lipids, but the molecular and cellular neurophysiology underlying these observations
is not known. Recent studies comparing dysregulated pathways in the peripheral nervous system (PNS) of
individuals with type II diabetic neuropathy highlighted alterations in lipid-sensor nuclear receptor, suggesting
a novel possible physiological basis for diabetic neuropathy. Our additional preliminary data suggest that
nuclear receptor LXRs expressed in sensory neurons may be involved. This project combines in vivo and in
vitro approaches to 1) study LXRs direct activation and as well as the downstream pathways regulated by
lipids in sensory neurons, 2) determine whether the LXR pathway contributes to type II diabetic neuropathy
in sensory neurons using a neuronal-specific deletion mouse model and high fat diet (HFD)-induced
neuropathy models (cre-lox model), 3) to determine if LXR agonist protect against HFD induced neuropathy
by regulating pathway(s) in the DRG small sensory neurons (RiboTag model). The central unifying
hypothesis is that activation of LXRs in PNS neurons regulates downstream LXR-dependent program to
maintain normal PNS function in the face of high-fat nutrition. Chronic rich lipid diets are expected to induce
LXR signaling alterations that lead to PNS dysfunction.
 These studies will begin to decipher the cellular, molecular, and physiological role of lipid-sensor nuclear
receptors in peripheral neurons in a type II diabetic mouse model. The results are expected to inform future
mechanistic research and drug development aimed at addressing the unmet clinical need to treat
neuropathy induced by obesity and its major complication, type II diabetes.

## Key facts

- **NIH application ID:** 9858323
- **Project number:** 5R01DK117404-03
- **Recipient organization:** LOYOLA UNIVERSITY CHICAGO
- **Principal Investigator:** Virginie Mansuy Aubert
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $371,069
- **Award type:** 5
- **Project period:** 2018-03-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858323

## Citation

> US National Institutes of Health, RePORTER application 9858323, Nuclear lipid-sensor in Type II Diabetic Neuropathy (5R01DK117404-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9858323. Licensed CC0.

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