ArticleJournal of animal science and biotechnology2020
Time-restricted feeding downregulates cholesterol biosynthesis program via RORγ-mediated chromatin modification in porcine liver organoids.
Article in Journal of animal science and biotechnology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- Epigenomic signatures of cis-regulatory elements in the developing mouse and pig forelimb.Scientific data · 2025Article
- Dietary Organic Zinc Supplementation Modifies the Oxidative Genes via RORγ and Epigenetic Regulations in the Ileum of Broiler Chickens Exposed to High-Temperature Stress.Antioxidants (Basel, Switzerland) · 2024Article
- Hepatic Anti-Oxidative GenesAntioxidants (Basel, Switzerland) · 2023Article
- Sodium butyrate alleviates deoxynivalenol-induced hepatic cholesterol metabolic dysfunction via RORγ-mediated histone acetylation modification in weaning piglets.Journal of animal science and biotechnology · 2022Article
- Dietary L-arginine supplementation of tilapia (Oreochromis niloticus) alters the microbial population and activates intestinal fatty acid oxidation.Amino acids · 2022Article
- Nuclear Receptor RORα/γ: Exciting Modulators in Metabolic Syndrome and Related Disorders.Frontiers in nutrition · 2022Review
- Aberrant Cholesterol Metabolic Genes Regulation in a Negative Feedback Loop Induced by an Alphacoronavirus.Frontiers in nutrition · 2022Article
- Orphan Nuclear Receptor RORγ Modulates the Genome-Wide Binding of the Cholesterol Metabolic Genes during Mycotoxin-Induced Liver Injury.Nutrients · 2021Article
- ROR: Nuclear Receptor for Melatonin or Not?Molecules (Basel, Switzerland) · 2021Review
- The Circadian Physiology: Implications in Livestock Health.International journal of molecular sciences · 2021Review
- Establishment of Functional Liver Spheroids From Human Hepatocyte-Derived Liver Progenitor-Like Cells for Cell Therapy.Frontiers in bioengineering and biotechnology · 2021Article
- DHCR24 in Tumor Diagnosis and Treatment: A Comprehensive Review.Technology in cancer research & treatmentReview
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTime-restricted feeding (TRF) is a dieting strategy based on nutrients availability and diurnal rhythm, shown to improve lipid metabolism efficiency. We have demonstrated previously that retinoic acid-related (RAR) orphan receptor (ROR) γ is the primary transcription factor controlling cholesterol (CHO) biosynthesis program of animals. However, the functional role of RORγ in liver physiology of pigs in response to TRF has not been determined, largely due to the lack of functional models and molecular tools. In the present study, we established porcine liver organoids and subjected them to restricted nutrients supply for 10-h during the light portion of the day.
resultsOur results showed that TRF regimen did not alter hepatocyte physiology, including unchanged cell viability, caspase 3/7 enzyme activity and the gene signature of cell proliferation in porcine liver organoids, compared to the control group (P > 0.05). Furthermore, we found that TRF downregulated the hepatic CHO biosynthesis program at both mRNA and protein levels, along with the reduced cellular CHO content in porcine liver organoids (P < 0.05). Using unbiased bioinformatic analysis of a previous ChIP-seq data and ChIP-qPCR validation, we revealed RORγ as the predominant transcription factor that responded to TRF, amongst the 12 targeted nuclear receptors (NRs) (P < 0.05). This was likely through RORγ direct binding to the MVK gene (encoding mevalonate kinase). Finally, we showed that RORγ agonists and overexpression enhanced the enrichment of co-factor p300, histone marks H3K27ac and H3K4me1/2, as well as RNA polymerase II (Pol-II) at the locus of MVK, in TRF-porcine liver organoids, compared to TRF-vector control (P < 0.05).
conclusionsOur findings demonstrate that TRF triggers the RORγ-mediated chromatin remodeling at the locus of CHO biosynthesis genes in porcine liver organoids and further improves lipid metabolism.
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