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Molecular control of systemic bile acid homeostasis by the liver glucocorticoid receptor.

Abstract：

:Systemic bile acid (BA) homeostasis is a critical determinant of dietary fat digestion, enterohepatic function, and postprandial thermogenesis. However, major checkpoints for the dynamics and the molecular regulation of BA homeostasis remain unknown. Here we show that hypothalamic-pituitary-adrenal (HPA) axis impairment in humans and liver-specific deficiency of the glucocorticoid receptor (GR) in mice disrupts the normal changes in systemic BA distribution during the fasted-to-fed transition. Fasted mice with hepatocyte-specific GR knockdown had smaller gallbladder BA content and were more susceptible to developing cholesterol gallstones when fed a cholesterol-rich diet. Hepatic GR deficiency impaired liver BA uptake/transport via lower expression of the major hepatocyte basolateral BA transporter, Na(+)-taurocholate transport protein (Ntcp/Slc10a1), which affected dietary fat absorption and brown adipose tissue activation. Our results demonstrate a role of the HPA axis in the endocrine regulation of BA homeostasis through the liver GR control of enterohepatic BA recycling.

journal_name

Cell Metab

journal_title

Cell metabolism

authors

Rose AJ,Berriel Díaz M,Reimann A,Klement J,Walcher T,Krones-Herzig A,Strobel O,Werner J,Peters A,Kleyman A,Tuckermann JP,Vegiopoulos A,Herzig S

doi

10.1016/j.cmet.2011.04.010

subject

Has Abstract

pub_date

2011-07-06 00:00:00

pages

123-30

issue

1

eissn

1550-4131

issn

1932-7420

pii

S1550-4131(11)00210-5

journal_volume

14

pub_type

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