The Bile Acid Chenodeoxycholic Acid Increases Human Brown Adipose Tissue Activity

The interest in brown adipose tissue (BAT) as a target to combat metabolic disease has recently been renewed with the discovery of functional BAT in humans. In rodents, BAT can be activated by bile acids, which activate type 2 iodothyronine deiodinase (D2) in BAT via the G-coupled protein receptor T...

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Published in:Cell metabolism Vol. 22; no. 3; p. 418
Main Authors: Broeders, Evie P M, Nascimento, Emmani B M, Havekes, Bas, Brans, Boudewijn, Roumans, Kay H M, Tailleux, Anne, Schaart, Gert, Kouach, Mostafa, Charton, Julie, Deprez, Benoit, Bouvy, Nicole D, Mottaghy, Felix, Staels, Bart, van Marken Lichtenbelt, Wouter D, Schrauwen, Patrick
Format: Journal Article
Language:English
Published: United States 01.09.2015
Subjects:
Adipocytes, Brown - drug effects
Adipocytes, Brown - metabolism
Adipose Tissue, Brown - drug effects
Adipose Tissue, Brown - metabolism
Administration, Oral
Adult
Cells, Cultured
Chenodeoxycholic Acid - administration & dosage
Chenodeoxycholic Acid - blood
Chenodeoxycholic Acid - pharmacology
Energy Metabolism - drug effects
Female
Humans
Receptors, G-Protein-Coupled - metabolism
Signal Transduction - drug effects
Young Adult
ISSN:1932-7420, 1932-7420
Online Access:Get more information
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Summary:The interest in brown adipose tissue (BAT) as a target to combat metabolic disease has recently been renewed with the discovery of functional BAT in humans. In rodents, BAT can be activated by bile acids, which activate type 2 iodothyronine deiodinase (D2) in BAT via the G-coupled protein receptor TGR5, resulting in increased oxygen consumption and energy expenditure. Here we examined the effects of oral supplementation of the bile acid chenodeoxycholic acid (CDCA) on human BAT activity. Treatment of 12 healthy female subjects with CDCA for 2 days resulted in increased BAT activity. Whole-body energy expenditure was also increased upon CDCA treatment. In vitro treatment of primary human brown adipocytes derived with CDCA or specific TGR5 agonists increased mitochondrial uncoupling and D2 expression, an effect that was absent in human primary white adipocytes. These findings identify bile acids as a target to activate BAT in humans.
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ISSN:1932-7420
1932-7420
DOI:10.1016/j.cmet.2015.07.002