Next Article in Journal
Whole-Grain Intake in the Mediterranean Diet and a Low Protein to Carbohydrates Ratio Can Help to Reduce Mortality from Cardiovascular Disease, Slow Down the Progression of Aging, and to Improve Lifespan: A Review
Previous Article in Journal
Nutritional Status of Children with Cerebral Palsy in Gorkha, Nepal: Findings from the Nepal Cerebral Palsy Register
 
 
Article

Orphan Nuclear Receptor RORγ Modulates the Genome-Wide Binding of the Cholesterol Metabolic Genes during Mycotoxin-Induced Liver Injury

Laboratory of Animal Physiology and Molecular Nutrition, Key Laboratory of Animal Breeding Reproduction and Molecular Design for Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Manuela Merli
Nutrients 2021, 13(8), 2539; https://doi.org/10.3390/nu13082539
Received: 10 June 2021 / Revised: 10 July 2021 / Accepted: 19 July 2021 / Published: 25 July 2021
(This article belongs to the Special Issue Nutrigenomic and Metabolism)
Maintaining lipid homeostasis is crucial to liver function, the key organ that governs the whole-body energy metabolism. In contrast, lipid dysregulation has been implicated in mycotoxin-induced liver injury, by which the pathophysiological regulation and the molecular components involved remain elusive. Here we focused on the potential roles of orphan nuclear receptor (NR) RORγ in lipid programming, and aimed to explore its action on cholesterol regulation in the liver of mycotoxin-exposed piglets. We found that liver tissues were damaged in the mycotoxin-exposed piglets compared to the healthy controls, revealed by histological analysis, elevated seral ALT, AST and ALP levels, and increased caspase 3/7 activities. Consistent with the transcriptomic finding of down-regulated cholesterol metabolism, we demonstrated that both cholesterol contents and cholesterol biosynthesis/transformation gene expressions in the mycotoxin-exposed livers were reduced, including HMGCS1, FDPS, SQLE, EBP, FDFT1 and VLDLR. Furthermore, we reported that RORγ binds to the cholesterol metabolic genes in porcine hepatocytes using a genome-wide ChIP-seq analysis, whereas mycotoxin decreased the RORγ binding occupancies genome-wide, especially at the cholesterol metabolic pathway. In addition, we revealed the enrichment of co-factors p300 and SRC, the histone marks H3K27ac and H3K4me2, together with RNA Polymerase II (Pol-II) at the locus of HMGCS1 in hepatocytes, which were reduced by mycotoxin-exposure. Our results provide a deep insight into the cholesterol metabolism regulation during mycotoxin-induced liver injury, and propose NRs as therapeutic targets for anti-mycotoxin treatments. View Full-Text
Keywords: RORγ; nuclear receptor; ChIP-seq; liver injury; mycotoxin; cholesterol biosynthesis RORγ; nuclear receptor; ChIP-seq; liver injury; mycotoxin; cholesterol biosynthesis
Show Figures

Figure 1

MDPI and ACS Style

Li, K.; Li, H.; Zhang, K.; Zhang, J.; Hu, P.; Li, Y.; Gu, H.; Liu, H.-Y.; Yang, Z.; Cai, D. Orphan Nuclear Receptor RORγ Modulates the Genome-Wide Binding of the Cholesterol Metabolic Genes during Mycotoxin-Induced Liver Injury. Nutrients 2021, 13, 2539. https://doi.org/10.3390/nu13082539

AMA Style

Li K, Li H, Zhang K, Zhang J, Hu P, Li Y, Gu H, Liu H-Y, Yang Z, Cai D. Orphan Nuclear Receptor RORγ Modulates the Genome-Wide Binding of the Cholesterol Metabolic Genes during Mycotoxin-Induced Liver Injury. Nutrients. 2021; 13(8):2539. https://doi.org/10.3390/nu13082539

Chicago/Turabian Style

Li, Kaiqi, Hao Li, Kexin Zhang, Jinying Zhang, Ping Hu, Yanwei Li, Haotian Gu, Hao-Yu Liu, Zhangping Yang, and Demin Cai. 2021. "Orphan Nuclear Receptor RORγ Modulates the Genome-Wide Binding of the Cholesterol Metabolic Genes during Mycotoxin-Induced Liver Injury" Nutrients 13, no. 8: 2539. https://doi.org/10.3390/nu13082539

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop