ArticleBMC molecular and cell biology2020
Retinoic acid receptor-related orphan receptor α reduces lipid droplets by upregulating neutral cholesterol ester hydrolase 1 in macrophages.
Article in BMC molecular and cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Identification of a spatially organized TREM2-associated permissive macrophage niche in human pulmonary tuberculosis alveolar pneumonia.Nature communications · 2026Article
- RORα: a critical nexus in the crosstalk between cholesterol metabolism and macrophage polarization.Frontiers in immunology · 2026Review
- Multi-omics insight into muscle quality divergence between high-altitude Bayinbuluke sheep and low-altitude Turpan black sheep.Frontiers in veterinary science · 2025Article
- Conserved transcription factors promote cell fate stability and restrict reprogramming potential in differentiated cells.Nature communications · 2023Article
- ISG15 Is a Novel Regulator of Lipid Metabolism duringMicrobiology spectrum · 2022Article
- KIAA1363-A Multifunctional Enzyme in Xenobiotic Detoxification and Lipid Ester Hydrolysis.Metabolites · 2022Review
- KIAA1363 affects retinyl ester turnover in cultured murine and human hepatic stellate cells.Journal of lipid research · 2022Article
- Nuclear Receptor RORα/γ: Exciting Modulators in Metabolic Syndrome and Related Disorders.Frontiers in nutrition · 2022Review
- Lipid Droplets, the Central Hub Integrating Cell Metabolism and the Immune System.Frontiers in physiology · 2021Review
- Orphan Nuclear Receptor RORα Regulates Enzymatic Metabolism of Cerebral 24S-Hydroxycholesterol through CYP39A1 Intronic Response Element Activation.International journal of molecular sciences · 2020Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundNeutral cholesterol ester hydrolase 1 (NCEH1) catalyzes the hydrolysis of cholesterol ester (CE) in macrophages. Genetic ablation of NCEH1 promotes CE-laden macrophages and the development of atherosclerosis in mice. Dysregulation of NCEH1 levels is involved in the pathogenesis of multiple disorders including metabolic diseases and atherosclerosis; however, relatively little is known regarding the mechanisms regulating NCEH1. Retinoic acid receptor-related orphan receptor α (RORα)-deficient mice exhibit several phenotypes indicative of aberrant lipid metabolism, including dyslipidemia and increased susceptibility to atherosclerosis.
resultsIn this study, inhibition of lipid droplet formation by RORα positively regulated NCEH1 expression in macrophages. In mammals, the NCEH1 promoter region was found to harbor putative RORα response elements (ROREs). Electrophoretic mobility shift, chromatin immunoprecipitation, and luciferase reporter assays showed that RORα binds and responds to ROREs in human NCEH1. Moreover, NCEH1 was upregulated through RORα via a phorbol myristate acetate-dependent mechanism during macrophage differentiation from THP1 cells. siRNA-mediated knockdown of RORα significantly downregulated NCEH1 expression and accumulated lipid droplets in human hepatoma cells. In contrast, NCEH1 expression and removal of lipid droplets were induced by RORα agonist treatments and RORα overexpression in macrophages.
conclusionThese data strongly suggested that NCEH1 is a direct RORα target, defining potential new roles for RORα in the inhibition of lipid droplet formation through NCEH1.
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