# The role of the SIRT1-LXR signaling axis in diabetes-induced cholesterol metabolism dysregulation

> **NIH NIH F32** · MICHIGAN STATE UNIVERSITY · 2020 · $69,306

## Abstract

Project Summary
 Diabetic retinopathy (DR) is a critical complication secondary to diabetes and is the
number one cause of blindness in adults worldwide. Despite recent advances using
pharmacotherapy, a cure for diabetic retinopathy has yet to be realized. Further understanding of
the molecular events that cause disease progression will allow for the development of novel
therapeutic solutions for this devastating disease. We believe that recent evidence from large
clinical trials demonstrating a strong association between lipid abnormalities and DR progression
as well as the discovery that pharmacological activation of liver X receptor (LXRα/LXRβ) prevents
DR in rodent models, offers a potential breakthrough in our search for cure of DR. To achieve this
goal, we propose to analyze retinal levels of SIRT1-LXR as well as investigate the impact DR has
on the SIRT1-LXR signaling axis. This signaling axis promotes activation of cholesterol
metabolism pathways as well as prevents upregulation of pro-inflammatory genes. Besides
measuring retinal levels of SIRT1 and LXR, we also propose to measure retinal cholesterol
metabolite leves in diabetic human cells as well as in an animal model of diabetes. This proposal
allows for the unique opportunity to characterize human donor retinas into distinct stages of DR
progression by using a novel imaging stitching software. This innovative imaging tool is readily
used in the Busik Laboratory to determine if donor retinas are in the early, non-proliferative stage
or are in the late, proliferative stage. Additionally, to ascertain if activation of this pathway is a
potential therapy for DR in vivo, we propose to analyze the effect of SIRT1-LXR activation in a
diabetic animal model. We hypothesize that activation of the SIRT1-LXR pathway will improve
the deleterious effects seen on retinal cholesterol metabolism and alleviate the inflammatory state
active in the diabetic milieu. Michigan State University is home to a world class Molecular
Metabolism and Disease Core. Thus, we propose to take advantage of this resources to further
characterize and analyze retinal cholesterol levels between control, early stages of DR as well as
late proliferate DR stages. Additionally, we currently have the tools necessary to activate the
SIRT1-LXR pathway in vivo, allowing us to determine if activation of the SIRT1-LXR pathway
prevents DR formation.

## Key facts

- **NIH application ID:** 9900014
- **Project number:** 5F32EY028426-03
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Sandra Suarez Hammer
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $69,306
- **Award type:** 5
- **Project period:** 2018-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900014

## Citation

> US National Institutes of Health, RePORTER application 9900014, The role of the SIRT1-LXR signaling axis in diabetes-induced cholesterol metabolism dysregulation (5F32EY028426-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9900014. Licensed CC0.

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