Bile acid synthesis in humans has a rapid diurnal variation that is asynchronous with cholesterol synthesis.
OBJECTIVE
The conversion of cholesterol to bile acids by the liver is an important regulator of body cholesterol homeostasis. In rodents, both cholesterol and bile acid synthesis have marked diurnal rhythms that peak synchronously at midnight. The aim of this study was to establish whether such diurnal rhythms are also present in healthy humans.


METHODS
Serum levels of the markers 7alpha-hydroxy-4-cholesten-3-one (C4) monitoring bile acid biosynthesis and lathosterol reflecting cholesterol synthesis were determined at 90-minute intervals in 8 human volunteers during standardized dietary conditions.


RESULTS
Serum C4 showed 2 distinct peaks (2- to 4-fold above baseline) during a 24-hour period, the first at 1:00 pm and the second at 9:00 pm. During the night, C4 levels declined, and they returned to baseline levels the next morning. In contrast, serum lathosterol levels peaked at night, between midnight and 4:00 am. The diurnal changes of C4 were not synchronous with serum lipid changes or with the postprandial increase in serum bile acids and were maintained in cholecystectomized subjects.


CONCLUSIONS
Bile acid synthesis in humans has a diurnal rhythm, with 2 peaks during the daytime, that is opposite from the circadian rhythm of cholesterol synthesis. This is completely different from the pattern in rodents and indicates the presence of an important species variation in the regulation of cholesterol homeostasis.
Gälman
Cecilia
C
Center for Metabolism and Endocrinology and Center for Nutrition and Toxicology, Department of Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden.
Angelin
Bo
B
Rudling
Mats
M
D000328:Adult; D001647:Bile Acids and Salts / Q000096:biosynthesis* / Q000097:blood*; D015415:Biomarkers / Q000378:metabolism; D002763:Cholecystectomy; D002783:Cholestenones / Q000097:blood; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood*; D002940:Circadian Rhythm / Q000502:physiology*; D005215:Fasting / Q000502:physiology; D005260:Female; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
D001647:Bile Acids and Salts; D015415:Biomarkers; D002783:Cholestenones; D014280:Triglycerides; C002656:7 alpha-hydroxy-4-cholesten-3-one; C001521:lathosterol; D002784:Cholesterol