The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 16 No. 8 • September 2013


How You, Too, May Benefit From the
New Research on DNA Methylation and
“Browning” of White Adipose Tissue

As we have been writing in recent newsletters, DNA methylation is a widely investigated way that gene transcription (expression or non-expression) is regulated. DNA hypermethylation seems to generally (but not always) suppress gene expression, whereas DNA hypomethylation generally (but not always) increases gene expression. Both EGCG and curcumin have been discovered to act as hypomethylation agents, that is, to decrease DNA methylation and to possibly increase gene expression. (See, for example, references 4 and 5 in the article above.)

A recent paper1 reports the good news that methylation of the UCP1 enhancer is responsible in mice adipose tissue for the regulation of UCP1 gene expression. This could be important because UCP1 (uncoupling protein 1) is a major genetic factor that is responsible for regulating thermogenesis (energy expenditure) in brown adipose tissue (brown fat). The fact that methylation controls the expression of UCP1 suggests that the use of demethylating agents such as EGCG or curcumin might increase its expression, at least in brown fat or “browned” white fat. The researchers1 found, in fact, that demethylation of the UCP1 promoter by the demethylating agent 5-aza-deoxycytidine increased UCP1 expression while methylation of UCP1 promoter-reporter constructs decreased expression.

It has been discovered that it is possible to cause white adipose tissue to become “browned,” (as discussed in the article above) that is to change its properties to more closely resemble brown adipose tissue. One of the most important of those changes is for adipocytes to become able to express Ucp1 and to engage in thermogenesis. We anticipate additional publications on the use of demethylating agents for the browning of white fat.

Reference

  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).

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