Circulating intestinal fibroblast growth factor 19 has a pronounced diurnal variation and modulates hepatic bile acid synthesis in man.
Bile acids (BAs) traversing the enterohepatic circulation exert several important metabolic effects. Their hepatic synthesis, controlled by the enzyme cholesterol 7alpha-hydroxylase (CYP7A1), has a unique diurnal variation in man. Here we provide evidence that the transintestinal flux of BAs regulates serum levels of intestinal fibroblast growth factor 19 (FGF19) that in turn modulate BA production in human liver. Basal FGF19 levels varied by 10-fold in normal subjects, and were reduced following treatment with a BA-binding resin and increased upon feeding the BA chenodeoxycholic acid. Serum FGF19 levels exhibited a pronounced diurnal rhythm with peaks occurring 90-120 min after the postprandial rise in serum BAs. The FGF19 peaks in turn preceded the declining phase of BA synthesis. The diurnal rhythm of serum FGF19 was abolished upon fasting. We conclude that, in humans, circulating FGF19 has a diurnal rhythm controlled by the transintestinal BA flux, and that FGF19 modulates hepatic BA synthesis. Through its systemic effects, circulating FGF19 may also mediate other known BA-dependent effects on lipid and carbohydrate metabolism.
Lundåsen
T
T
Metabolism Unit, Department of Endocrinology, Metabolism and Diabetes, Center for Nutrition and Toxicology, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Gälman
C
C
Angelin
B
B
Rudling
M
M
D001647:Bile Acids and Salts / Q000096:biosynthesis* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D002792:Cholestyramine Resin / Q000494:pharmacology; D002940:Circadian Rhythm / Q000502:physiology*; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood*; D005765:Gastrointestinal Agents / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008102:Liver Circulation / Q000502:physiology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis
D001647:Bile Acids and Salts; D015415:Biomarkers; C117476:FGF19 protein, human; D005765:Gastrointestinal Agents; D012333:RNA, Messenger; D002635:Chenodeoxycholic Acid; D002792:Cholestyramine Resin; D005346:Fibroblast Growth Factors; D002790:Cholesterol 7-alpha-Hydroxylase