ArticleJCI insight2020
Selective LXR agonist DMHCA corrects retinal and bone marrow dysfunction in type 2 diabetes.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 35 citations in OpenAlex.
- Long-Acting RXR Agonism Preserves Retinal Function and Modulates Inflammation in Diabetic Retinopathy.Diabetes · 2026Article
- Article
- Lipid homeostasis plays a critical role in inherited and acquired retinal diseases.Communications biology · 2026Review
- Resilient Calvarial Bone Marrow Supports Retinal Repair in Type 2 Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nuclear Receptor-Targeted Therapies: Reprogramming Metabolism with TRβ, ERRα, and LXR Modulators.Biomolecules · 2026Review
- Understanding the link between lipid and ocular disorders for effective therapy.Archives of medical science : AMS · 2026Article
- Review
- In search of nonlipogenic ABCA1 inducers (NLAI): precision coregulator TR-FRET identifies diverse signatures for LXR ligands.bioRxiv : the preprint server for biology · 2025Article
- Impact of Donor and Host Age on Systemic Cell Therapy to Treat Age-Related Macular Degeneration.Cells · 2025Article
- Role of Brain Liver X Receptor in Parkinson's Disease: Hidden Treasure and Emerging Opportunities.Molecular neurobiology · 2024Review
- N,N-Dimethyl-3β-hydroxycholenamide attenuates neuronal death and retinal inflammation in retinal ischemia/reperfusion injury by inhibiting Ninjurin 1.Journal of neuroinflammation · 2023Article
- Intravitreal Administration of AAV2-SIRT1 Reverses Diabetic Retinopathy in a Mouse Model of Type 2 Diabetes.Translational vision science & technology · 2023Article
- Liver X Receptor Regulation of Glial Cell Functions in the CNS.Biomedicines · 2022Review
- Lipids, hyperreflective crystalline deposits and diabetic retinopathy: potential systemic and retinal-specific effect of lipid-lowering therapies.Diabetologia · 2022Review
- Depleting hypothalamic somatostatinergic neurons recapitulates diabetic phenotypes in mouse brain, bone marrow, adipose and retina.Diabetologia · 2021Article
- Nuclear receptors in the kidney during health and disease.Molecular aspects of medicine · 2021Review
- Reverse Cholesterol Transport Pathway and Cholesterol Efflux in Diabetic Retinopathy.Journal of diabetes research · 2021Review
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
In diabetic dyslipidemia, cholesterol accumulates in the plasma membrane, decreasing fluidity and thereby suppressing the ability of cells to transduce ligand-activated signaling pathways. Liver X receptors (LXRs) make up the main cellular mechanism by which intracellular cholesterol is regulated and play important roles in inflammation and disease pathogenesis. N, N-dimethyl-3β-hydroxy-cholenamide (DMHCA), a selective LXR agonist, specifically activates the cholesterol efflux arm of the LXR pathway without stimulating triglyceride synthesis. In this study, we use a multisystem approach to understand the effects and molecular mechanisms of DMHCA treatment in type 2 diabetic (db/db) mice and human circulating angiogenic cells (CACs), which are hematopoietic progenitor cells with vascular reparative capacity. We found that DMHCA is sufficient to correct retinal and BM dysfunction in diabetes, thereby restoring retinal structure, function, and cholesterol homeostasis; rejuvenating membrane fluidity in CACs; hampering systemic inflammation; and correcting BM pathology. Using single-cell RNA sequencing on lineage-sca1+c-Kit+ (LSK) hematopoietic stem cells (HSCs) from untreated and DMHCA-treated diabetic mice, we provide potentially novel insights into hematopoiesis and reveal DMHCA's mechanism of action in correcting diabetic HSCs by reducing myeloidosis and increasing CACs and erythrocyte progenitors. Taken together, these findings demonstrate the beneficial effects of DMHCA treatment on diabetes-induced retinal and BM pathology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.