Time-restricted feeding downregulates cholesterol biosynthesis program via ROR?-mediated chromatin modification in porcine liver organoids.

ABSTRACT: Background: Time-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) ? is the primary transcription factor controlling cholesterol (CHO) biosynthesis program of animals. However, the functional role of ROR? 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.

Results: Our 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?
Conclusions: Our findings demonstrate that TRF triggers the ROR?-mediated chromatin remodeling at the locus of CHO biosynthesis genes in porcine liver organoids and further improves lipid metabolism.

SUBMITTER: Zhang K 

PROVIDER: S-EPMC7604961 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature