Highlights From the Latest in Diabetes Research

In 2009–2010, 78 million U.S. adults aged 320 years were obese—a number representing 35.7% of the adult population. As the prevalence of obesity continues its alarming rise among both adults and children, the need for novel approaches to prevention and treatment is increasingly urgent. New research from the Spiegelman laboratory contributes to the growing body of literature concerning the potential therapeutic implications of “beige” adipocyte regulation. It is well established that white adipose tissue primarily functions in energy storage (triglycerides) and as an endocrine organ (adipokines), whereas brown adipose tissue generates heat and plays an important role in maintaining energy homeostasis. Mice that are genetically manipulated to have higher levels of brown fat also have more pronounced antiobesity and antidiabetic profi les. The current study shows that a third class of adipocytes (beige) is present within white adipose tissue depots, that beige adipocytes have a gene expression pattern that is distinct from both brown and white adipocytes, and that beige adipocytes are derived from a unique precursor population. In an initial series of experiments in mice, the researchers show that beige adipocytes have a low basal expression of UCP1 that is similar to white adipose tissue, but when stimulated, UCP1 levels increase as much as 150-fold, resulting in an absolute level of UCP1 similar to that observed in brown adipose tissue. Additional experiments showed that irisin, a hormone that is secreted by muscle and upregulated during exercise in a manner that results in the “browning” of white adipose tissue, selectively upregulated UCP1 genes in beige adipocyte precursors, suggesting that these precursor cells are sensitive to the browning effects of irisin. Finally, data from brown adipose tissue biopsies of two independent human cohorts showed that brown adipose tissue had gene expression signatures resembling beige cells in mice and that UCP1-positive cells had the same beige cell markers observed in mice. These results indicate that what has previously been thought of as brown fat in humans has characteristics that are more similar to murine beige fat. These data offer insights into how regulation of this new class of adipocytes might be harnessed for development of novel therapies to fi ght the obesity epidemic. — Helaine E. Resnick, PhD, MPH