Complex interaction between circadian rhythm and diet on bile acid homeostasis in male rats.
Level 5 - mechanism / opinion, no new human data
Animal laboratory experiment
PubMed 29028359 · doi:10.1080/07420528.2017.1363226
What was done
Male Wistar rats were evaluated across two experiments to determine how meal timing and dietary composition interact with circadian rhythms to affect bile acid homeostasis. In experiment 1, rats were subjected to three feeding schedules (24-hour ad libitum, 10-hour dark-phase restricted, or 10-hour light-phase restricted) combined with three diets (standard chow, free-choice high-fat-high-sugar, or free-choice high-fat). In experiment 2, rats on standard chow received either ad libitum feeding or a six-meals-a-day schedule. Plasma bile acid levels, pool composition, and hepatic mRNA expression of bile acid synthesis and regulatory genes (Cyp7a1, Cyp8b1, Shp) were measured at eight time points across 24 hours.
What was found
The abstract reports no numerical values, effect sizes, or confidence intervals. Total plasma bile acid concentrations peaked during fasting periods and decreased upon food consumption across all diets. Time-restricted feeding enhanced daily plasma bile acid rhythms. A high-fat diet altered bile acid pool composition but maintained daily rhythmicity of total concentrations. Hepatic Cyp7a1 and Cyp8b1 mRNA rhythms aligned with the hepatic molecular clock, while Shp expression was driven primarily by food intake. Combining a high-fat diet with light-period (inactive phase) feeding abolished Cyp7a1 and Cyp8b1 expression rhythms while preserving Shp rhythmicity. Inactive-phase feeding altered bile acid pool composition similarly to high-fat feeding.
Why it matters
This work shows that circulating bile acid dynamics and key hepatic synthetic enzymes are differentially entrained by nutritional timing versus the autonomous hepatic molecular clock. It demonstrates that mistimed eating during the resting phase can disrupt metabolic gene rhythms and mimic the compositional bile acid shifts induced by high-fat diets.
Limits
This was an animal study conducted exclusively in male Wistar rats, limiting direct translation to human circadian physiology. Group sample sizes (n) were not reported in the abstract. The abstract omitted numerical concentrations, variances, and statistical values. Female animals were not investigated.
Cited by
- supports Time-restricted feeding upregulates a liver enzyme that converts cholesterol into bile acids, reducing liver cholesterol and increasing bile acid production.