The effects of oral administration of bile salt hydrolase on the partition of fatty acid and glucose oxidation in Zucker fatty rats (585.8)

Abstract

Conjugated bile salts take part in micellar formation, a critical step for dietary lipid digestion and absorption. Bile salt hydrolases (BSHs) catalyze the conversion of conjugated bile salts to bile acids and amino acids. Gut bacteria produce this family of enzymes. BSHs could potentially reduce the efficiency of lipid digestion and absorption if applied to the upper portion of the small intestine. Thus, we hypothesize that BSH is a novel lead for therapeutic reduction of lipid absorption needed to control obesity in humans. To test this, recombinant BSH (rBSH) was expressed and purified from an E. coli expression system by Ni‐NTA affinity chromatography. The rBSH or bovine serum albumin (BSA) control (2.7mg/kg of body weight) was gavaged daily into Zucker fatty (ZF) rats (9‐12 weeks old, 4 per group) just before the start of the dark photoperiod (before active feeding starts) for 7 days. After the last treatment, rats were housed individually in Comprehensive Laboratory Animal Monitoring Systems for 24 hours to collect the indirect calorimetry data. The rats treated with rBSH had significantly higher respiratory exchange ratios (RER) during the dark (p=0.028), but not the light photoperiod. The heat production and change in body weight were not different between groups. The higher RER data of ZF rats treated with rBSH during the dark photoperiod (feeding time) indicate a reduction of energy derived from fat oxidation, suggesting that lipid digestion or absorption may be reduced, which leads to higher utilization of glucose. Together, the findings shown in this pilot study suggest BSH is a lead for novel medication for modulating lipid digestion and absorption.