The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 17 No. 5 • June 2014


INCREASING THERMOGENESIS OF
BROWN FAT WITH A SUPPLEMENT

Uncoupling Protein 1 (Ucp1) Increases Energy Expenditure in Brown Adipose Tissue

Possible Induction of Expression of Ucp1 With EGCG or Curcumin

A recent paper1 reports increased expression of the thermogenesis gene Ucp1 (uncoupling protein 1) that increases energy expenditure in brown fat with a demethylating drug, 5-aza-deoxycytidine. This proof of principle paper suggests that other demethylating agents, such as EGCG (the major green tea catechin) and curcumin (found in turmeric root) may also have this effect. If so, it provides evidence of a potential mechanism to support the use of EGCG and curcumin in weight control regimens.

One of the distinguishing features of brown fat as compared to white fat is that brown fat, but not white fat, contains Ucp1 and when activated (by adrenergic stimulation1B or exposure to cold) burns off fat to generate heat, a process called thermogenesis. The Ucp1 is called an uncoupling protein because the way it works is by disengaging the oxidative phosphorylation that would otherwise take place in mitochondria to produce ATP to the use of that fuel to create heat.1

The authors1 report data in this study that shows that demethylation of the Ucp1 promoter by the drug 5-aza-deoxycytidine results in increased expression of Ucp1. They also report that there is a silencing modification on the Ucp1 enhancer in white fat, while a marker indicating activation appears on the Ucp1 promoter in brown fat in response to a cold environment. The control of whether a gene is turned on or off by methylation in genes or histones is called epigenetics. The silencing feature in the Ucp1 gene in white fat is essential to white fat acting as a “thrifty” store of fuel for when food is scarce.

This discovery is very important because for a long time scientists have been studying how to cause white fat to undergo “browning,” natural processes that stimulate white fat to express some of the properties of brown fat, especially the all-important energy expenditure that helps eliminate excess storage of white fat and its associated negative effects on health. In fact, it has been found possible to produce “browning” of white fat to become more like brown fat.1C,1D But increasing the expression of Ucp1 to increase energy expenditure in brown fat via an epigenetic mechanism is a different way of increasing energy expenditure to help prevent obesity and its associated disorders (e.g., type 2 diabetes). Importantly, this method may be easier at present with the availability of safe-to-use natural products that have been shown to act as demethylating agents.1F,1G

References

1. Shore et al. Role of Ucp1 enhancer methylation and chromatin remodelling in the control of Ucp1 expression in murine adipose tissue. Diabetologia. 53:1164-73 (2010).
1B. Inokuma et al. Indispensable role of mitochondrial UCP1 for antiobesity effect of beta3-adrenergic stimulation. Am J Physiol Endocrinol Metab. 290:E1014-21 (2006).
1C. Fisher et al. FGF21 regulates PGC-1alpha and browning of white adipose tissues in adaptive thermogenesis. Genes Dev. 26:271-81 (2012).
1D. Mitschke et al. Increased cGMP promotes healthy expansion and browning of white adipose tissue. FASEB J. 27:1621-30 (2013).
1E. Liu et al. Curcumin is a potent DNA hypomethylation agent. Bioorg Med Chem Lett. 19:706-9 (2009).
1F. Fang et al. Tea polyphenol (-)-Epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res. 63:7563-70 (2003).

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