Abstract
Background & AimsIt is not known how hepatic bile acids transport kinetics changes postprandially in the intact liver. We used positron emission tomography (PET)/computed tomography (CT) with the tracer [N-methyl-11C]cholylsarcosine (11C-CSar), a synthetic sarcosine conjugate of cholic acid, to quantify fasting and postprandial hepatic bile acid transport kinetics in healthy human participants.MethodsSix healthy human participants underwent dynamic liver 11C-CSar PET/CT (60 min) during fasting and from 15 min after ingestion of a standard liquid meal. Hepatobiliary secretion kinetics of 11C-CSar was calculated from PET data, blood samples (arterial and hepatic venous) and hepatic blood flow measured using indocyanine green infusion.ResultsIn the postprandial state, hepatic blood perfusion increased on average by 30% (p <0.01), and the flow-independent hepatic intrinsic clearance of 11C-CSar from blood into bile increased by 17% from 1.82 (range, 1.59–2.05) to 2.13 (range, 1.75–2.50) ml blood/min/ml liver tissue (p = 0.042). The increased intrinsic clearance of 11C-CSar was not caused by changes in the basolateral clearance efficacy of 11C-CSar but rather by an upregulated apical transport, as shown by an increase in the rate constant for apical secretion of 11C-CSar from hepatocyte to bile from 0.40 (0.25–0.54) min−1 to 0.67 (0.36–0.98) min−1 (p = 0.03). This resulted in a 33% increase in the intrahepatic bile flow (p = 0.03).ConclusionsThe rate constant for the transport of bile acids from hepatocytes into biliary canaliculi and the bile flow increased significantly in the postprandial state. This reduced the mean 11C-CSar residence time in the hepatocytes.Lay summaryBile acids are important for digestion of dietary lipids including vitamins. We examined how the secretion of bile acids by the liver into the intestines changes after a standard liquid meal. The transport of bile acids from liver cells into bile and bile flow was increased after the meal.
Highlights
Bile acids are produced in the hepatocytes and secreted across the apical membrane into the biliary canaliculi by active transport[1] and flow with bile into the gut
Hepatic venous blood had a higher concentration of 11C-CSar, likely as a result of increased hepatic blood flow, but not enough to affect the hepatic extraction fractions as described
Kinetics for the uptake of 11C-CSar from blood to hepatocyte Neither E0 nor EAUC was statistically significantly different when comparing the postprandial and fasting states (Table 2), there was a trend towards a decrease in EAUC (p = 0.054)
Summary
Bile acids are produced in the hepatocytes and secreted across the apical membrane into the biliary canaliculi by active transport[1] and flow with bile into the gut. Bile acids are important for absorption of dietary lipids and lipophile substances.[2] The intestinal uptake of bile acids, which primarily takes place in the terminal ileum, is highly efficient and facilitated by active transmembrane transport proteins.[3] After absorption, the bile acids are returned by the portal venous system to the liver where they are removed from the blood and subsequently secreted into the biliary tree This enterohepatic circulation of bile acids depends strongly on an intact and adaptive transhepatic bile acid transport and secures a high bile acid concentration in the gut with little de novo synthesis.[4,5]. Recent surgery to the biliary system with cholecystectomy together with the collection of bile from an invasive catheter that may disturb the enterohepatic circulation of bile acids could have altered the physiology of bile formation and flow It is not known how hepatic bile acids transport kinetics changes postprandially in the intact liver.
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