Hepatic bile acid transport increases in the postprandial state: A functional ¹¹C-CSar PET/CT study in healthy humans

TY - JOUR

T1 - Hepatic bile acid transport increases in the postprandial state

T2 - A functional 11C-CSar PET/CT study in healthy humans

AU - Ørntoft, Nikolaj W

AU - Gormsen, Lars C

AU - Keiding, Susanne

AU - Munk, Ole L

AU - Ott, Peter

AU - Sørensen, Michael

N1 - © 2021 The Authors.

PY - 2021/6

Y1 - 2021/6

N2 - Background & Aims: It 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. Methods: Six 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. Results: In 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). Conclusions: The 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 summary: Bile 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.

AB - Background & Aims: It 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. Methods: Six 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. Results: In 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). Conclusions: The 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 summary: Bile 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.

KW - Hepatobiliary kinetics

KW - Liver physiology

KW - Positron emission tomography

UR - http://www.scopus.com/inward/record.url?scp=85107274731&partnerID=8YFLogxK

U2 - 10.1016/j.jhepr.2021.100288

DO - 10.1016/j.jhepr.2021.100288

M3 - Journal article

C2 - 34095797

SN - 2589-5559

VL - 3

JO - JHEP Reports

JF - JHEP Reports

IS - 3

M1 - 100288

ER -