The Secret Life of Fat Suggests New Therapeutic Targets

Abstract

Not so many years ago, most considered fat a passive recipient of our indulgence. But since the discovery of leptin in 1994,1 it has become ever clearer that fat is more than a storage site for excess calories. Rather, fat plays an active, communicative role in metabolism that research is beginning to uncover. Two recent studies not only represent our rapidly changing grasp of the biology of fat but also suggest potential treatments for one of the world's most intractable chronic health conditions: obesity. A paper in Nature 2 in January 2012 from the laboratory of Bruce Spiegelman, PhD, of the Dana-Farber Cancer Institute in Boston, MA, reported the discovery of a new hormone released by muscle that converts white fat deposits into thermogenic brown fat. Whereas white fat acts as a repository for excess, mitochondria-rich brown fat cells burn ordinary fat as energy to produce heat. Once thought to only exist in rodents and infants, several groups have confirmed brown fat in humans. It is found in small patches along the spine, in the upper back, on the sides of the neck, and between the collarbone and shoulder. A few weeks after Spiegelman's Nature paper was published, a publication3 in the Journal of Clinical Investigation from the laboratory of Shelia Collins, PhD, of the Sanford-Burnham Medical Research Institute in Orlando, FL, revealed the heart plays a role in the regulation of fat burning. Collins, first author Marica Bordicchia, and colleagues reported that cardiac natriuretic peptides increased browning of white fat, elevating uncoupling protein 1 (UCP1)–dependent energy expenditure. C. Ronald Kahn, MD, chief academic officer at the Joslin Diabetes Center in Boston, MA, says the recent discoveries are likely just the opening act in our growing knowledge about fat metabolism. “Right now we're looking at the first things …