A Pro-Drug Strategy Enhances Butyrate Bioavailability and Therapeutic Efficacy In Atherosclerosis
Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B954
Abstract ID: 5126
Presenting Author:
Taryn N Beckman , PhD Candidate at Univ. of Chicago, Univ. of Chicago Pritzker Sch. of Molecular Engr.
Abstract:
Butyrate is a gut microbiota derived short chain fatty acid with pleiotropic positive effects on inflammation and metabolism. In atherosclerosis, sodium butyrate has been shown to significantly reduce atherosclerotic lesions, rectify routine metabolic parameters such as LDL-C in the serum, and reduce systemic inflammation. However, its foul odor, low absorption, and fast metabolism limit its therapeutic effectiveness. We engineered a derivate of butyrate attached to the amino acid serine (SerBut) to mask the taste and odor and co-opt amino acid transporters in the gut to increase its bioavailability. In Vitro, SerBut maintains the anti-inflammatory, NFkB suppressing, capacity of sodium butyrate while allowing higher dosing without inducing cytotoxicity. SerBut can be stably, easily, and odorlessly administered in drinking water at higher doses than previously possible. Over 6 weeks of HFD in concurrence with SerBut water, SerBut reduces LDL-C in the serum, plaque accumulation in the aortic root, and monocytes in the aorta of an apolipoprotein-E-/- murine model of atherosclerosis. Bioinformatic analysis of fecal 16S rRNA sequencing reveals Seryl modification of butyrate to be associated with less plaque in the aortic root of mice, while general butyrate treatment was not. SerBut reduces enzymes associated with liver damage and has a systemic tolerogenic effect. SerBut is a promising therapeutic that lowers lipids and lipid driven inflammation without inducing liver toxicity.
A Pro-Drug Strategy Enhances Butyrate Bioavailability and Therapeutic Efficacy In Atherosclerosis
Category
Late Breaking Abstracts