Page 80 - Human Bile Acid Metabolism: a Postprandial Perspective

Chapter 4
peak levels, energy expenditure went down. Additionally, BA levels and energy expenditure were not correlated (data not shown), demonstrating that the change in BA in our study did not modulate energy expenditure directly or later after the meal. The timing of the energy expenditure measurements did not coincide with the peak in bile acid levels in our studies, which may explain why there was no discernible effect. This does mean that postprandial BA concentrations are unlikely to play a large role in physiological control of total daily energy expenditure. Supra-physiological stimuli might be capable of enhancing energy expenditure, as proposed recently by Broeders and colleagues [28]. Strengths of this study include the paired design, allowing for a relative small sample size and the use of more sensitive statistical methods, the longer timeframe of postprandial plasma sampling compared to previous studies using mixed-meal testing, and the highly sensitive HPLC-MSMS method for measuring all physiologically relevant BA. Limitations of the study include the fact that we did not perform clamp studies to assess insulin sensitivity since we were interested in the postprandial BA curve. Additionally, the gut microbiome may have been altered by the dietary intervention. Finally, our intervention may not have been long enough to change BA levels profoundly. DCA constitutes a large part of the BA pool. Although we have previously seen acute meal effects on postprandial BA curves (unpublished data), slow changes in the composition of the BA pool and a presumably intact negative feedback mechanism via FXR may explain only a modest change after ~11 days of hypocaloric feeding in our subjects.
In conclusion, a short-duration very low calorie diet modestly increased the DCA component of the postprandial BA response in obese subjects while decreasing energy expenditure. Changes in activity of BA transporters, CYP8B1 and the gut microbiome may be involved in this response.
Statement of authorship
FSvN designed the study, performed clinical experiments, laboratory and statistical analyses, and wrote and edited the manuscript. MRS designed the study, reviewed and edited the manuscript. FGS and WK performed laboratory analyses and reviewed the manuscript. JAR and SWOD reviewed the manuscript.
78