Cholestyramine treatment of healthy humans rapidly induces transient hypertriglyceridemia when treatment is initiated.

Abstract

Bile acid (BA) production in mice is regulated by hepatic farnesoid X receptors and by intestinal fibroblast growth factor (FGF)-15 (in humans, FGF-19), a suppressor of BA synthesis that also reduces serum triglycerides and glucose. Cholestyramine treatment reduces FGF-19 and induces BA synthesis, whereas plasma triglycerides may increase from unclear reasons. We explored whether FGF-19 may suppress BA synthesis and plasma triglycerides in humans by modulation of FGF-19 levels through long-term cholestyramine treatment at increasing doses. In a second acute experiment, metabolic responses from 1 day of cholestyramine treatment were monitored. Long-term treatment reduced serum FGF-19 by >90%; BA synthesis increased up to 17-fold, whereas serum BAs, triglycerides, glucose, and insulin were stable. After long-term treatment, serum BAs and FGF-19 displayed rebound increases above baseline levels, and BA and cholesterol syntheses normalized after 1 wk without rebound reductions. Acute cholestyramine treatment decreased FGF-19 by 95% overnight and serum BAs by 60%, while BA synthesis increased fourfold and triglycerides doubled. The results support that FGF-19 represses BA synthesis but not serum triglycerides. However, after cessation of both long-term and 1-day cholestyramine treatment, circulating FGF-19 levels were normalized within 2 days, whereas BA synthesis remained significantly induced in both situations, indicating that also other mechanisms than the FGF-19 pathway are responsible for stimulation of BA synthesis elicited by cholestyramine. Several of the responses during cholestyramine treatment persisted at least 6 days after treatment, highlighting the importance of removing such treatment well before evaluating dynamics of the enterohepatic circulation in humans.

• Authors: Beatrice G Sjöberg, Sara Straniero, Bo Angelin, Mats Rudling
• Journal: American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 313 Issue 2 Pg. E167-E174 (08 01 2017) ISSN: 1522-1555 [Electronic] United States
• PMID: 28487440 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 the American Physiological Society.

Chemical References

• Bile Acids and Salts
• FGF19 protein, human
• Triglycerides
• Cholestyramine Resin
• Fibroblast Growth Factors

Topics

• Adult
• Bile Acids and Salts (metabolism)
• Cholestyramine Resin (administration & dosage, adverse effects)
• Dose-Response Relationship, Drug
• Female
• Fibroblast Growth Factors (blood)
• Healthy Volunteers
• Humans
• Hypertriglyceridemia (chemically induced, metabolism)
• Liver (metabolism)
• Male
• Time Factors
• Triglycerides (metabolism)