title: Plasma bile acids are not associated with energy metabolism in humans.
abstract: Bile acids (BA) have recently been shown to increase energy expenditure in mice, but this concept has not been tested in humans. Therefore, we investigated the relationship between plasma BA levels and energy expenditure in humans. Type 2 diabetic (T2DM) patients (n = 12) and gender, age and BMI-matched healthy controls (n = 12) were studied before and after 8 weeks of treatment with a BA sequestrant. In addition, patients with liver cirrhosis (n = 46) were investigated, since these display elevated plasma BA together with increased energy expenditure. This group was compared to gender-, age- and BMI-matched healthy controls (n = 20). Fasting plasma levels of total BA and individual BA species as well as resting energy expenditure were determined. In response to treatment with the BA sequestrant, plasma deoxycholic acid (DCA) levels decreased in controls (-60%, p < 0.05) and T2DM (-32%, p < 0.05), while chenodeoxycholic acid (CDCA) decreased in controls only (-33%, p < 0.05). Energy expenditure did not differ between T2DM and controls at baseline and, in contrast to plasma BA levels, was unaffected by treatment with the BA sequestrant. Total BA as well as individual BA species did not correlate with energy expenditure at any time throughout the study. Patients with cirrhosis displayed on average an increase in energy expenditure of 18% compared to values predicted by the Harris-Benedict equation, and plasma levels of total BA (up to 12-fold) and individual BA (up to 20-fold) were increased over a wide range. However, neither total nor individual plasma BA levels correlated with energy expenditure. In addition, energy expenditure was identical in patients with a cholestatic versus a non-cholestatic origin of liver disease while plasma total BA levels differed four-fold between the groups. In conclusion, in the various (patho)physiological conditions studied, plasma BA levels were not associated with changes in energy expenditure. Therefore, our data do not support an important role of circulating BA in the control of human energy metabolism.
authors.affiliation: Dept. of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
authors.forename: Gemma
authors.initials: G
authors.lastname: Brufau
authors.affiliation: Dept. of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Bahr
authors.affiliation: Univ. Lille Nord de France, F-59000, Lille, France.|Institut Pasteur de Lille, F-59019, Lille, France.|INSERM U1011, F-59019, Lille, France.|UDSL, F-59000, Lille, France.
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.affiliation: Dept. of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
authors.forename: Thierry
authors.initials: T
authors.lastname: Claudel
authors.affiliation: Dept. of Gastroenterology, Hepatology and Endocrinology, Klinikum Bremen-Mitte, Bremen, Germany.
authors.forename: Johann
authors.initials: J
authors.lastname: Ockenga
authors.affiliation: Dept. of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Klaus Hw
authors.initials: KH
authors.lastname: Böker
authors.affiliation: Kinemed, Inc., Emeryville, CA, USA.|Dept. of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Murphy
authors.affiliation: Kinemed, Inc., Emeryville, CA, USA.
authors.forename: Kris
authors.initials: K
authors.lastname: Prado
authors.affiliation: Dept. of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
authors.forename: Frans
authors.initials: F
authors.lastname: Stellaard
authors.affiliation: Dept. of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.affiliation: Dept. of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.|Dept. of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
authors.forename: Folkert
authors.initials: F
authors.lastname: Kuipers
authors.affiliation: Dept. of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.|Dept. of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Uwe Jf
authors.initials: UJ
authors.lastname: Tietge
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