Chrono-metabolic regulation of hepatic fibrosis via NR1D1-mediated hepatic stellate cell activation

Table 1 Key circadian regulators in hepatic stellate cell activation and liver fibrosis

Circadian gene/regulator	Model/cell type	Intervention/condition	Main findings	Mechanistic insight	Ref.
NR1D1/Rev-erbα	Mouse liver, HSCs	Circadian disruption/CCl4	Dysregulated NR1D1/Rev-erbα; enhanced HSC activation	Loss of NR1D1 promotes TGF-β signaling and ECM deposition	[1,10,20,24]
BMAL1	HSCs, LX2 cells	TGF-β1 induction	Downregulated BMAL1; increased glycolysis and HSC activation	BMAL1 inhibits phenotypic transformation via IDH1/α-KG-mediated glycolysis	[23,38,40]
CLOCK, Per1-3	HSCs	CCl4-induced fibrosis	Reduced CLOCK gene expression	Disruption of CC contributes to HSC proliferation and collagen synthesis	[18,21,37]
REV-ERBα	HSCs, mice	Melatonin/SR9009	Upregulation prevented HSC activation	Modulates circadian clock and PPARα signaling	[18,39]

This table summarizes the primary circadian clock components involved in hepatic stellate cell activation and hepatic fibrosis, including experimental models, interventions, main findings, mechanistic insights, and supporting references. HSC: Hepatic stellate cell; CC: Circadian clock; TGF-β: Transforming growth factor-beta; ECM: Extracellular matrix.