The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 18 No. 8 • December 2015

Bile Acids Induce Expression of Genes in Brown Fat That Increase Metabolic Rate (Thermogenesis)

The physiological functions of bile acids have been found to extend beyond that of regulating the absorption and catabolism (breakdown) of fats such as cholesterol and triglycerides. It is reportedly involved in the liver’s metabolism of fatty acid and triglyceride synthesis and VLDL (very low density lipoproteins) production mediated by sterol-regulatory-element-binding protein 1c and bile acids have been shown to inhibit high fat diet induced hyperglycemia and obesity in C57BL/6J mice (Ikemoto, 1997). Not too long ago, a paper (Watanabe, 2006) reported that bile acids increased energy expenditure in brown fat (this was in mice) and prevented obesity and insulin resistance. Remarkably, they found that cholic acid, a bile acid, induced the enzyme (D2, iodothyronine deiodinase type 2) that converts the biologically inactive thyroid hormone T4 to its active form T3. Cholic acid increased D2 activity and oxygen consumption in brown fat, preventing obesity and increasing fat oxidation (thus increasing insulin sensitivity). Incidentally, as an aside, niacin (via the pulsatile release of prostaglandin D2) also increases the oxidation of fats by signaling the conversion of cellular energy use from glucose to fats (Virtue, 2012); this appears to be one of the mechanisms by which niacin beneficially affects the metabolism of lipids.

Iodothyronine diodinase type 2 (D2) is also expressed in skeletal muscle. The researchers (Watanabe, 2006) found that skeletal muscle cells from the mice treated with cholic acid also had increased D2 activity and therefore served as a source of the active form of thyroid hormone.

D2 Is a Selenoprotein

One way to improve the function of D2 is to take adequate amounts of selenium as the enzyme is a selenoprotein (Curcio, 2001). Inadequate selenium intake is one way that people can be hypothyroid even when they secrete adequate amounts of T4 because D2 is needed to convert that T4 to its active form T3.


  • Curcio et al. The human type 2 iodothyronine deiodinase is a selenoprotein highly expressed in a mesothelioma cell line. J Biol Chem. 276:30183-7 (2001).
  • Watanabe, Houten, Mataki, et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature. 439:484-9 (2006).
  • Ikemoto, Takahashi, Tsunoda, et al. Cholate inhibits high-fat diet-induced hyperglycemia and obesity with acyl-CoA synthetase mRNA decrease. Am J Physiol. 273 (Endocrinol Metab 36): E37-E45 (1997).
  • Virtue, Feldmann, Christian, et al. A new role for lipocalin prostaglandin D synthase in the regulation of brown adipose tissue substrate utilization. Diabetes. 61:3139-47 (2012).

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