Abstract 16849: Mice Lacking Cyp8b1 Have Dramatically Improved Cardio-Metabolic Profile Due to Alterations in Bile Acid Profile

Bile acids are important amphoteric biomolecules that can serve in a variety of biological functions including; fat emulsification and molecular signaling via nuclear receptors. Bile acid synthesis mediated via CYP7A1is the primary route for excess cholesterol elimination. The major bile acids in humans are cholic acid (CA) and chenodeoxycholic acids (CDCA). CYP8B1 is part of the family of CYP P450 enzymes. CYP8B1 is expressed in the endoplasmic reticulum as a membrane protein which is responsible for the catalysis of 7α-hydroxy-4cholesten-3-one (7-HCO) into 7-12- α-dihydroxy-4-cholesten-3-one (7-12 diHCO) both being rate-limiting step intermediates of bile acid (BA) synthesis. We hypothesized that CYP8B1 KO mice would have several favorable cardiometabolic changes due to improved BA profile. CYP8B1 KO mice lack CA resulting in a 50% decrease in cholesterol absorption as determined by dual isotope kinetics. These mice also have increased fecal excretion of total-bile acids (~300%) and cholesterol (40%). E...