Page 78 - Human Bile Acid Metabolism: a Postprandial Perspective

Chapter 4
Discussion
Here, we studied the effects of dietary short-term weight loss on plasma BA composition in obese insulin resistant subjects. The 3-day eucaloric period following the hypocaloric diet phase allowed us to isolate the effects of weight loss from the generally insulin desensitizing effects of prolonged energy deficit [22]. We found that among BA, dietary weight loss by VLCD in this study modestly increased only postprandial peak levels of deoxycholic acid. Figure 2 suggests higher BA concentrations in the first hour after the test meal, but this was not found to be significant (data not shown).
Postprandial BA levels in the systemic circulation are determined by the uptake rate from the gut and hepatic uptake from the portal vein. Uptake from the gut is by passive and active transluminal transport, where the latter depends on the ileal enterocytic BA transporter apical sodium-dependent BA transporter (ASBT) [23]. Hepatic uptake from the portal blood relies on expression of Na+-taurocholate co-transporting polypeptide (NTCP) and members of the organic anion transport family. Hepatic uptake via NTCP has a substrate preference for trihydroxylated (i.e. CA in humans) over dihydroxylated BA (i.e. CDCA and DCA), and for conjugated over unconjugated BA as reported by Hofmann [24]. A preferential decrease in DCA uptake over other BA therefore seems unlikely; thus the DCA specific increase in our study may be attributed to an increased DCA uptake from the gut.
The modest increase of peak DCA levels that we found is supported by different studies that have shown DCA responsiveness to different interventions [4,6,25]. Increased gut DCA uptake can be explained by a variety of non-mutually exclusive ways. First, the proportion of DCA in the total BA pool could be increased, similar to the BA pool of patients with T2DM. That in turn leads to increased postprandial DCA concentrations in plasma. The changes in the circulating BA pool could be driven by changes in the microbiome under the influence of caloric restriction, leading to increased rates of conversion of CA into DCA. That would also explain why the increase in DCA was mainly composed of unconjugated DCA (Supplementary Table S1). The early phase of the postprandial bile acid response reflects the influx of bile acids that are stored in the intestine in the fasting state. We showed previously that vancomycin treatment selectively modulated the gut
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