Natural polyketide enterocin inhibits ASGR1 to enhance cholesterol efflux and regulate hepatic lipid metabolism

Enterocin significantly reduced visceral and subcutaneous fat in HFD-fed wild-type mice while improving serum lipid profiles.

• Enterocin enhanced cholesterol efflux in liver cells by binding to ASGR1 and promoting its degradation.
• Activation of AMPKα and upregulation of cholesterol efflux were observed following ASGR1 inhibition.
• In mouse models, enterocin lowered total cholesterol (TC), triglycerides (TG), and LDL cholesterol (LDL-C), while increasing HDL cholesterol (HDL-C).
• The degradation of ASGR1 was confirmed to depend on the proteasome, as shown by the effects of specific inhibitors.
• Enterocin's lipid-lowering effects were comparable or superior to atorvastatin in HFD-fed LDLR mice.
• No significant impact on intestinal fat absorption was noted, indicating enterocin's targeted action on liver cholesterol metabolism.

AI simplified