The Bile Acid Chenodeoxycholic Acid Increases Human Brown Adipose Tissue Activity

• Published in: Cell metabolism Vol. 22; no. 3; pp. 418 - 426
• 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 Elsevier Inc 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: 1550-4131; 1932-7420; 1932-7420
• DOI: 10.1016/j.cmet.2015.07.002

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. [Display omitted] •The bile acid CDCA increases human BAT activity•CDCA increases mitochondrial uncoupling in human primary adipocytes derived from BAT•CDCA promotes mitochondrial uncoupling via TGR5 While cold is an effective strategy to activate brown fat, alternative approaches are warranted. Broeders et al. show that the bile acid chenodeoxycholic acid (CDCA) promotes mitochondrial uncoupling via TGR5 in human brown adipocytes and increases brown fat activity and energy expenditure in women.