Unlocking thermogenic silencers for the treatment of metabolic disease

Since the discovery that individuals with active brown adipose tissue (BAT) have lower prevalence of cardiometabolic diseases, it has been hypothesized that this depot can be targeted to improve human metabolic health. A major limitation with BAT, however, is that it is silenced under physiological temperatures, and the mechanisms that restrict its activation are not completely elucidated. To unlock the true potential of BAT, it is critical to understand the mechanisms governing its silencing. Herein, we provide an integrated review of the main regulatory factors that suppress thermogenic adipocytes, which we have termed 'thermogenic silencers', and present a series of perspectives to position thermogenic silencers as novel targets for the improvement of metabolic health in humans.