A Scalable COF-Based Sequestrant for Synergistic Bile Acid Modulation in Fatty Liver Disease

Area of Science:

• Materials Science
• Hepatology
• Biochemistry

Background:

• Metabolic dysfunction-associated fatty liver disease (MAFLD) is a growing clinical concern, often linked to disrupted cholesterol metabolism and bile acid (BA) imbalances.
• Current treatments like cholestyramine have limitations, including targeting only deprotonated BAs and causing nutrient loss.

Purpose of the Study:

• To develop a novel oral adsorbent for MAFLD treatment using a covalent organic framework (COF) platform.
• To evaluate the COF's efficacy in adsorbing both protonated and deprotonated bile acids selectively.

Main Methods:

• Development of a stable, olefin-linked covalent organic framework (COF) for synergistic anion-exchange and pore-adsorption.
• In vitro and in vivo validation of the COF's adsorbent performance compared to cholestyramine.
• Assessment of COF treatment in a high-fat-diet-induced MAFLD mouse model over 10 weeks.

Main Results:

• The COF adsorbent demonstrated superior performance in adsorbing both deprotonated and protonated BAs, surpassing cholestyramine and avoiding nutrient adsorption.
• COF treatment in MAFLD mice significantly reduced serum total cholesterol and LDL cholesterol.
• Marked alleviation of hepatic steatosis, inflammation, and liver injury markers was observed in treated mice.

Conclusions:

• Covalent organic frameworks (COFs) represent a promising next-generation oral adsorbent material for MAFLD.
• This study provides a mechanistic framework for utilizing molecularly engineered materials to target metabolic disorders like MAFLD.