Editors' ChoiceMetabolism

Bile acids go up to BAT

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Science Translational Medicine  19 Aug 2015:
Vol. 7, Issue 301, pp. 301ec141
DOI: 10.1126/scitranslmed.aad0229

Considered a “holy grail” by virtue of its calorie-burning properties, brown adipose tissue (BAT) consists of highly metabolically active fat depots that are rich in mitochondria. Because BAT is found in humans, there is great interest in boosting its activity to rev up metabolism. Although cold exposure activates BAT, most of us would rather not spend our days shivering in the cold, so the search for other BAT activators continues. One candidate that increases BAT activity in mice is bile acids, which are essential for lipid digestion and cholesterol excretion and have roles in substrate metabolism.

In a new proof-of-concept study, Broeders et al. determined whether supplementation with the bile acid chenodeoxycholic acid (CDCA) had the same BAT-activating effect in humans as it does in mice. In a crossover design, 12 healthy females were given 15 mg/kg of oral CDCA or placebo for two consecutive days. Treatment with CDCA increased resting metabolic rate by 5%, although 24-hour energy expenditure measured in a whole room calorimeter did not change. PET-CT scan imaging of BAT depot regions (neck, thorax, and abdomen) revealed more BAT activity, as measured by radiolabeled glucose uptake, after CDCA treatment than after placebo. The increase, however, was not nearly as high as that produced by cold exposure. In complementary experiments, BAT was biopsied from surgical patients, and the adipocytes were treated with CDCA, increasing mitochondrial respiration, uncoupling protein 1 expression, and increasing activity of the TGR5 signaling pathway. Taken together, these findings suggest that BAT can be activated in humans by bile acid supplementation and likely by other agonists of TGR5. Longer-term studies are needed to establish whether the effects are sustained, and these molecules can be used therapeutically to help mitigate obesity and related metabolic disorders.

E. P. M. Broeders et al., The bile acid chenodeoxycholic acid increases human brown adipose tissue activity. Cell Metab. 22, 1–9 (2015). [Abstract]

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