Pronounced variation in bile acid synthesis in humans is related to gender, hypertriglyceridaemia and circulating levels of fibroblast growth factor 19

Abstract

Background: Bile acid (BA) synthesis is essential in cholesterol and lipid homoeostasis.

Methods: Serum samples from 435 normal and 23 cholecystectomized subjects were obtained after overnight fasting and assayed for markers of BA and cholesterol synthesis, as well as cholesterol absorption. We determined whether BA synthesis was related to fibroblast growth factor 19 (FGF19; a circulating metabolic regulator that is thought to inhibit BA synthesis), gender, age and serum lipids.

Results: Bile acid synthesis varied more than 9-fold in normal individuals and was 29% higher in men than in women. Whilst low-density lipoprotein cholesterol increased with age, BA and cholesterol synthesis were stable. BA production was positively correlated with serum triglycerides (TGs), and 35% of individuals with a high level (>95th percentile) of BA synthesis had hypertriglyceridaemia (HTG) (>95th percentile). Serum FGF19 levels varied by 7-fold in normal individuals and were related inversely to BA synthesis but were not related to gender, plasma lipids or history of cholecystectomy.

Conclusions: Bile acid synthesis has a wide inter-individual variation, is lower in women than in men and is correlated positively with serum TGs. High BA production is frequently linked to HTG. Age-related hypercholesterolaemia is not associated with changes in BA or cholesterol production, nor to an increase in cholesterol absorption. In humans, the circulating level of FGF19 may regulate hepatic BA production under fasting conditions.