Programming of initial steps in bile acid synthesis by breast-feeding vs. formula-feeding in the baboon

Abstract

We tested the hypothesis that breast- vs. formula-feeding differentially affects the enzymatic activity of three sterol hydroxylases critical in the initial steps of bile acid formation. Thirty baboons were either breast-fed or formula-fed for the first 14 wk of life before weaning to baboon chow. At 14 and 34 wk of age, liver biopsies were assayed for cholesterol 7alpha-hydroxylase (CYP7A1), 27-hydroxycholesterol-7alpha-hydroxylase (CYP7B1), and cholesterol 27-hydroxylase (CYP27A1). We also determined the kinetics of 3H-27-hydroxycholesterol (27-OHC) turnover in vivo at both ages. At 14 wk of age, hepatic CYP7A1 activity was low but sevenfold higher among formula-fed vs. breast-fed baboons. By 34 wk, CYP7A1 activity had increased nearly 10-fold in both infant diet groups, and the sevenfold difference in CYP7A1 between previously breast- and formula-fed animals persisted. There were no differences in CYP7B1 activities between infant diet groups at either 14 or 34 wk of age although the activity increased in both groups by about 50% from 14 to 34 wk. CYP27A1 activity also increased between 14 and 34 wk of age, and, compared with CYP7A1, relatively small differences in CYP27A1 activity due to infant diet were observed at each age. Plasma 27-OHC turnover had a half-time of 2-4 min. We had previously reported that after weaning, the total bile acid synthesis rate was higher among baboons that were formula-fed than among breast-fed animals. The present results suggest that this difference is most likely due to significantly higher CYP7A1 activity among formula-fed vs. breast-fed animals.