ArticleJournal of lipid research2014
A novel posttranscriptional mechanism for dietary cholesterol-mediated suppression of liver LDL receptor expression.
Article in Journal of lipid research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Residual atherosclerotic cardiovascular disease risk in statin-treated patients: mechanisms, therapeutic strategies, and future directions-a scoping review.Frontiers in cardiovascular medicine · 2026Pooled it
- Blood-Based α-Synuclein Biomarkers in Parkinson's Disease: Molecular Diversity, Analytical Advances and Clinical Translation.International journal of molecular sciences · 2026Review
- DN203316, a novel PPARδ agonist, suppresses ferroptotic signaling and fibrogenesis in metabolic dysfunction-associated steatohepatitis.Experimental & molecular medicine · 2026Article
- Sulfur-Rich Garlic Extract (DNR) as a Promising Natural Therapeutic for Diabetic Nephropathy: Evidence from aInternational journal of molecular sciences · 2025Article
- A molecular tango between chromatin and metabolites orchestrates a feedback switch for alcohol consumption.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Pathways and Molecular Mechanisms Governing LDL Receptor Regulation.Circulation research · 2025Review
- Unlocking Cholesterol Metabolism in Metabolic-Associated Steatotic Liver Disease: Molecular Targets and Natural Product Interventions.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Article
- Gut ribotoxic stress responses facilitate dyslipidemia via metabolic reprogramming: an environmental health prediction.Theranostics · 2024Article
- Cold shock domain-containing protein E1 is a posttranscriptional regulator of the LDL receptor.Science translational medicine · 2022Article
- Dietary cholesterol promotes growth and ecdysone signalling pathway by modulating cholesterol transport in swimming crabs (Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2022Article
- Sex-specific alterations in hepatic cholesterol metabolism in low birth weight adult guinea pigs.Pediatric research · 2022Article
- Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression.Nature genetics · 2021Article
- Triciribine Engages ZFP36L1 and HuR to Stabilize LDLR mRNA.Molecules (Basel, Switzerland) · 2020Article
- Running Head: Heat Affects Cholesterol and Bile Acid Alterations in Cholesterol and Bile Acids Metabolism in Large White Pigs during Short-Term Heat Exposure.Animals : an open access journal from MDPI · 2020Article
- Liver-specific knockdown of long-chain acyl-CoA synthetase 4 reveals its key role in VLDL-TG metabolism and phospholipid synthesis in mice fed a high-fat diet.American journal of physiology. Endocrinology and metabolism · 2019Article
- Farnesoid X Receptor Activation by Obeticholic Acid Elevates Liver Low-Density Lipoprotein Receptor Expression by mRNA Stabilization and Reduces Plasma Low-Density Lipoprotein Cholesterol in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- A comparison of effects of DPP-4 inhibitor and SGLT2 inhibitor on lipid profile in patients with type 2 diabetes.Lipids in health and disease · 2017Observational
- A novel peroxisome proliferator response element modulates hepatic low-density lipoprotein receptor gene transcription in response to PPARδ activation.The Biochemical journal · 2015Article
- High-fructose feeding promotes accelerated degradation of hepatic LDL receptor and hypercholesterolemia in hamsters via elevated circulating PCSK9 levels.Atherosclerosis · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
It is well-established that over-accumulation of dietary cholesterol in the liver inhibits sterol-regulatory element binding protein (SREBP)-mediated LDL receptor (LDLR) gene transcription leading to a reduced hepatic LDLR mRNA level in hypercholesterolemic animals. However, it is unknown whether elevated cholesterol levels can elicit a cellular response to increase LDLR mRNA turnover to further repress LDLR expression in liver tissue. In the current study, we examined the effect of a high cholesterol diet on the hepatic expression of LDLR mRNA binding proteins in three different animal models and in cultured hepatic cells. Our results demonstrate that high cholesterol feeding specifically elevates the hepatic expression of LDLR mRNA decay promoting factor heterogeneous nuclear ribonucleoprotein (HNRNP)D without affecting expressions of other LDLR mRNA binding proteins in vivo and in vitro. Employing the approach of adenovirus-mediated gene knockdown, we further show that depletion of HNRNPD in the liver results in a marked reduction of serum LDL-cholesterol and a substantial increase in liver LDLR expression in hyperlipidemic mice. Additional studies of gene knockdown in albumin-luciferase-untranslated region (UTR) transgenic mice provide strong evidence supporting the essential role of 3'UTR in HNRNPD-mediated LDLR mRNA degradation in liver tissue. Altogether, this work identifies a novel posttranscriptional regulatory mechanism by which dietary cholesterol inhibits liver LDLR expression via inducing HNRNPD to accelerate LDLR mRNA degradation.
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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.