TY - JOUR
T1 - Plasma Bile Acids Are Associated with Energy Expenditure and Thyroid Function in Humans
AU - Ockenga, Johann
AU - Valentini, Luzia
AU - Schuetz, Tatjana
AU - Wohlgemuth, Franziska
AU - Glaeser, Silja
AU - Omar, Ajmal
AU - Kasim, Esmatollah
AU - duPlessis, Daniel
AU - Featherstone, Karen
AU - Davis, Julian R.
AU - Tietge, Uwe J. F.
AU - Kroencke, Thomas
AU - Biebermann, Heike
AU - Koehrle, Josef
AU - Brabant, Georg
PY - 2012/2
Y1 - 2012/2
N2 - Background/Aims: Animal studies implicate a role of bile acids (BA) in thyroid-regulated energy expenditure (EE) via activation of the TGR-5/adenylate cyclase/deiodinase type 2 pathway. Here we investigated these possible associations in humans.Methods: EE, BA, and thyroid hormone status were assessed in 10 healthy subjects and eight patients with liver cirrhosis at baseline and after oral nutrition. In cirrhosis, blood was additionally sampled from the mesenteric vein and the radial artery.Results: At baseline, BA and EE related positively (r = 0.648, P = 0.048 in healthy subjects; r = 0.833, P = 0.010 in cirrhosis; r = 0.556, P = 0.017 in all), with the highest correlation with deoxycholic acid levels. The respiratory quotient associated negatively to baseline BA (all, r = -0.639, P = 0.004). Postprandially, serum TSH decreased in both groups (P <0.05 each). In cirrhosis, the decrease of TSH after 60 min correlated to the meal-stimulated BA increase (r = -0.762, P = 0.028). To assess the mechanism involved, we studied a single human TSHoma and T alpha T1 mouse thyrotrope cells. In TSHoma cells, TGR-5 was predominantly expressed cytoplasmically, and in vitro stimulation with BA did not substantially alter cAMP or deiodinase type 2.Conclusions: Our data support a role of BA in human energy metabolism and in thyroid hormone control. Even though no convincing response to BA was demonstrated in TSHoma and T alpha T1 cells, the TSH decrease after a nutritional challenge suggests an interaction of BA on the set point of the thyroid axis. (J Clin Endocrinol Metab 97:535-542, 2012)
AB - Background/Aims: Animal studies implicate a role of bile acids (BA) in thyroid-regulated energy expenditure (EE) via activation of the TGR-5/adenylate cyclase/deiodinase type 2 pathway. Here we investigated these possible associations in humans.Methods: EE, BA, and thyroid hormone status were assessed in 10 healthy subjects and eight patients with liver cirrhosis at baseline and after oral nutrition. In cirrhosis, blood was additionally sampled from the mesenteric vein and the radial artery.Results: At baseline, BA and EE related positively (r = 0.648, P = 0.048 in healthy subjects; r = 0.833, P = 0.010 in cirrhosis; r = 0.556, P = 0.017 in all), with the highest correlation with deoxycholic acid levels. The respiratory quotient associated negatively to baseline BA (all, r = -0.639, P = 0.004). Postprandially, serum TSH decreased in both groups (P <0.05 each). In cirrhosis, the decrease of TSH after 60 min correlated to the meal-stimulated BA increase (r = -0.762, P = 0.028). To assess the mechanism involved, we studied a single human TSHoma and T alpha T1 mouse thyrotrope cells. In TSHoma cells, TGR-5 was predominantly expressed cytoplasmically, and in vitro stimulation with BA did not substantially alter cAMP or deiodinase type 2.Conclusions: Our data support a role of BA in human energy metabolism and in thyroid hormone control. Even though no convincing response to BA was demonstrated in TSHoma and T alpha T1 cells, the TSH decrease after a nutritional challenge suggests an interaction of BA on the set point of the thyroid axis. (J Clin Endocrinol Metab 97:535-542, 2012)
KW - BROWN ADIPOSE-TISSUE
KW - METABOLISM
KW - RECEPTOR
KW - IDENTIFICATION
KW - NUTRITION
KW - PITUITARY
U2 - 10.1210/jc.2011-2329
DO - 10.1210/jc.2011-2329
M3 - Article
SN - 0021-972X
VL - 97
SP - 535
EP - 542
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 2
ER -