Diurnal rhythms of bile acid production in the rat

Abstract

Diurnal rhythms of bile acid synthesis were studied in Sprague-Dawley rats maintained in 12 h of illumination and 12 h of darkness each day. Synthesis, measured as output from a chronic bile fistula, underwent a consistent diurnal change with an amplitude of about 20% around mean daily synthesis and a peak in the dark period. The peak in cholate synthesis preceded the peak in chenodeoxycholate synthesis which preceded the peak in alpha-muricholate synthesis which preceded the peak in beta-muricholate synthesis. Fasting, intravenous infusion of dexamethasone (100 microgram/kg . h), adrenalectomy, and ocular enucleation all failed to abolish the diurnal rhythm in synthesis. In one rat studied 30 days after ocular enucleation the diurnal rhythm in synthesis persisted; however, relative to 4 days after enucleation the phase of the rhythm shifted about 90 degrees suggesting that light deprivation caused the rhythm to become free-running with a period slightly different from 24 h.

Regulation of bile acid synthesis in man. Presence of a diurnal rhythm.

“…In contrast, humans have diurnal rhythms that generally peak between 6 a.m. and 12 noon (32). It is not surprising, therefore, that our observed diurnal rhythm in bile acid synthesis peaked at about 9 a.m. Amplitude of the diurnal rhythm in our subjects was ±35-55%, which is similar to the amplitude of the rhythm of bile acid production in the rat (12,15).…”

“…For purposes of the present study, we are not forced to assume that "4C released from [26-'4C] In the rat, diurnal rhythm of bile acid production and activity of 7a-hydroxylase have an acrophase at about 10 p.m. (11,12). Because the rat is a nocturnal animal, acrophases of most of its diurnal rhythms occur in the evening hours.…”

“…Indeed, the basis for most diurnal rhythms has been difficult to clearly define. Diurnal rhythms usually persist for at least some length of time when rhythmic environmental clues, e.g., eating and light cycles, are removed (12,33). Such clues, however, may serve to entrain the rhythm to a given period and acrophase.…”

“…First, fasting, which is associated with a decreased flux of bile acid through the liver, reduces bile acid synthesis and 7a-hydroxylase activity (10,11). Second, bile acid synthesis and 7a-hydroxylase activity undergo a diurnal rhythm with peak activity during the waking and feeding hours (11,12) when hepatic flux of bile acid is also highest (13). We have demonstrated effects of fasting on synthesis in man as well as in animal models (10,12).…”

“…Second, bile acid synthesis and 7a-hydroxylase activity undergo a diurnal rhythm with peak activity during the waking and feeding hours (11,12) when hepatic flux of bile acid is also highest (13). We have demonstrated effects of fasting on synthesis in man as well as in animal models (10,12). However, the diurnal rhythm of bile acid synthesis has never been studied in humans with an intact enterohepatic circulation because of technical difficulties in making many measurements of synthesis over a 24-h period.…”