Figure 1.
Scheme of major components of the enterohepatic circulation (EHC) of bile acids (BAs) in mice.
Primary BAs are synthesized and conjugated by the liver and released into the intestine lumen to aid nutrient absorption. The majority of BAs are reabsorbed by intestinal transporters Asbt (apical) and Ostα/β (basolateral) into portal venous blood. A small portion of BAs are deconjugated by bacteria in distal ileum and further dehydroxylated or epimerized by bacteria in the large intestine to generate secondary BAs. Deconjugated primary and secondary BAs can be passively diffused into the portal blood. Ntcp is the major transporter in the liver that removes the majority of BAs from portal blood. Unconjugated BAs are taken up by organic anion transporting polypeptide 1b2 (Oatp1b2) on the basolateral membrane of hepatocytes or passive absorption. Upon entering hepatocytes, unconjugated and secondary BAs are reconjugated and rehydroxylated before they are pumped into the bile by Bsep to start another EHC. Under normal conditions, BAs are synthesized in pericentral hepatocytes, whereas BAs are taken up by periportal hepatocytes. Nuclear receptor FXR coordinates BA homeostasis by promoting (arrow) or repressing (blunt arrow) of key BA synthesis enzymes or transporters in liver and ileum. Bold arrows indicate the BA flows.
Figure 2.
Circadian fluctuations of serum total BAs, as well as secondary transformation and conjugations in control-fed (Ctrl) and cholestyramine-fed (Resin) mice.
Tauro-BAs: tauro-conjugated BAs; Glyco-BAs: glycine-conjugated BAs; Unconj-BAs: unconjugated BAs. Shaded area of the figure represents dark phase and opened area stands for light phase. Data are presented as mean ± standard error (n = 5). Asterisk stands for statistically difference between control and resin groups. p≤0.05, student t-test (two-tailed). Same illustrations apply to the following figures.
Figure 3.
Diurnal fluctuations of individual BAs in mouse serum under control- or resin-fed conditions.
Each individual BA includes both taurine-conjugated and unconjugated forms.
Figure 4.
Changes of BA composition in mouse serum by cholestyramine in the morning (10:00) and evening (22:00).
Each individual BA includes both taurine-conjugated and unconjugated forms.
Figure 5.
Circadian fluctuations of liver total BAs, as well as secondary transformation and conjugations in control- and resin-fed mice.
Figure 6.
Diurnal fluctuations of individual BAs in mouse liver under control- or resin-fed conditions.
Each individual BA includes both taurine-conjugated and unconjugated forms.
Figure 7.
Changes of BA composition in mouse serum by cholestyramine in the morning (10:00) and evening (22:00).
Each individual BA includes both taurine-conjugated and unconjugated forms.
Figure 8.
Circadian expression of hepatic and ileal genes in control- and resin-fed mice.
(A) Circadian expression profiles of FXR in liver and Ileum, (B) hepatic genes, and (C) ileal genes under control- and resin-fed conditions.
Figure 9.
Comparing mRNAs of key hepatic and ileal BA-metabolism genes from 10:00 to 22:00 in wild-type (WT; n = 5) and FXR-null (n = 4) mice.
Asterisk stands for statistically difference between wild-type and FXR-null.