Hannah M Eggink1, F Samuel van Nierop1, Marieke G Schooneman1, Anita Boelen1, Andries Kalsbeek2, Martijn Koehorst3, Gabriella A M Ten Have4, L Maurits de Brauw5, Albert K Groen6, Johannes A Romijn7, Nicolaas E P Deutz4, Maarten R Soeters8. 1. Department of Endocrinology and Metabolism, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. 2. Department of Endocrinology and Metabolism, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands; Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands. 3. Department of Pediatrics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. 4. Centre for Translational Research in Aging and Longevity, Dept. Health and Kinesiology, Texas A & M University, College Station, United States. 5. Department of Surgery, MC Slotervaart, Amsterdam, The Netherlands. 6. Department of Pediatrics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands; Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. 7. Department of Internal Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. 8. Department of Endocrinology and Metabolism, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: http://metabolism.maartensoeters.nl.
Abstract
BACKGROUND & AIMS: Bile acids (BAs) play a key role in lipid uptake and metabolic signalling in different organs including gut, liver, muscle and brown adipose tissue. Portal and peripheral plasma BA concentrations increase after a meal. However, the exact kinetics of postprandial BA metabolism have never been described in great detail. We used a conscious porcine model to investigate postprandial plasma concentrations and transorgan fluxes of BAs, glucose and insulin using the para-aminohippuric acid dilution method. METHODS: Eleven pigs with intravascular catheters received a standard mixed-meal while blood was sampled from different veins such as the portal vein, abdominal aorta and hepatic vein. To translate the data to humans, fasted venous and portal blood was sampled from non-diabetic obese patients during gastric by-pass surgery. RESULTS: The majority of the plasma bile acid pool and postprandial response consisted of glycine-conjugated forms of primary bile acids. Conjugated bile acids were more efficiently cleared by the liver than unconjugated forms. The timing and size of the postprandial response showed large interindividual variability for bile acids compared to glucose and insulin. CONCLUSIONS: The liver selectively extracts most BAs and BAs with highest affinity for the most important metabolic BA receptor, TGR5, are typically low in both porcine and human peripheral circulation. Our findings raise questions about the magnitude of a peripheral TGR5 signal and its ultimate clinical application.
BACKGROUND & AIMS:Bile acids (BAs) play a key role in lipid uptake and metabolic signalling in different organs including gut, liver, muscle and brown adipose tissue. Portal and peripheral plasma BA concentrations increase after a meal. However, the exact kinetics of postprandial BA metabolism have never been described in great detail. We used a conscious porcine model to investigate postprandial plasma concentrations and transorgan fluxes of BAs, glucose and insulin using the para-aminohippuric acid dilution method. METHODS: Eleven pigs with intravascular catheters received a standard mixed-meal while blood was sampled from different veins such as the portal vein, abdominal aorta and hepatic vein. To translate the data to humans, fasted venous and portal blood was sampled from non-diabetic obesepatients during gastric by-pass surgery. RESULTS: The majority of the plasma bile acid pool and postprandial response consisted of glycine-conjugated forms of primary bile acids. Conjugated bile acids were more efficiently cleared by the liver than unconjugated forms. The timing and size of the postprandial response showed large interindividual variability for bile acids compared to glucose and insulin. CONCLUSIONS: The liver selectively extracts most BAs and BAs with highest affinity for the most important metabolic BA receptor, TGR5, are typically low in both porcine and human peripheral circulation. Our findings raise questions about the magnitude of a peripheral TGR5 signal and its ultimate clinical application.
Authors: Samuel A J Trammell; Jens S Svenningsen; Jens J Holst; Matthew P Gillum; Rune E Kuhre Journal: Molecules Date: 2020-05-20 Impact factor: 4.411
Authors: Fianne L P Sips; Hannah M Eggink; Peter A J Hilbers; Maarten R Soeters; Albert K Groen; Natal A W van Riel Journal: Front Physiol Date: 2018-06-08 Impact factor: 4.566
Authors: Vanessa Baier; Henrik Cordes; Christoph Thiel; José V Castell; Ulf P Neumann; Lars M Blank; Lars Kuepfer Journal: Front Physiol Date: 2019-09-27 Impact factor: 4.566
Authors: Emma C E Meessen; Fianne L P Sips; Hannah M Eggink; Martijn Koehorst; Johannes A Romijn; Albert K Groen; Natal A W van Riel; Maarten R Soeters Journal: Physiol Rep Date: 2020-03