The anti-aging compound resveratrol is sometimes described as an attempt at delivering the benefits of caloric restriction in pill form.

Now, scientists may have identified a companion compound that delivers the benefits of exercise in a pill. In the Jan. 12, 2012, edition of Nature, scientists have reported that rodents treated with a newly identified signaling hormone, irisin, lost weight and improved their blood sugar control.

If they pan out, the findings would certainly make for easier-to-keep New Year's resolutions. 2012's "Eat less and exercise more" could conceivably be replaced by 2022's "get prescriptions for resveratrol and irisin."

In a nutshell, the authors reported in their paper that irisin is produced by muscle cells during exercise, and stimulates the conversion of white to brown fat cells. Brown fat, which burns energy instead of storing it, was once thought to exist only in hibernating animals and newborn humans. But more recent research has shown that adult humans, too, still have some brown fat – and that increasing the number of those fat cells might have positive effects on weight and metabolism.

In 2009, Bruce Spiegelman and his colleagues published work showing how to convert white to brown fat by engineering certain transcription factors into immature cells that could induce them to become brown fat cells. (See BioWorld Today, July 30, 2009.)

At that point, Spiegelman said finding a signaling hormone that could induce the switch from white to brown fat cells "is reasonable to think that it might provide a direct anti-obesity treatment."

In the new paper, Spiegelman – who is again the senior author – and his team showed that irisin fits the bill for such a hormone. In their experiments, Spiegelman and his team started by looking at which genes were influenced by a transcription activator that is known to mediate some of the beneficial effects of exercise: PGC1-alpha. Among the genes they identified was the membrane protein FNDC5. Part of the full-length FNDC5, in turn, is cut and secreted from the membrane as a signaling hormone – which Spiegelman and his team named irisin after the Greek messenger goddess Iris.

Sedentary, obese mice that were treated with irisin for 10 days improved their blood sugar and glucose values, and lost some weight. The work has obvious commercial potential, and that potential is being tapped by Boston-based start-up Ember Therapeutics Inc. The company was co-founded by Spiegelman.

"There are two brown fat cell lineages," Ember president and interim CEO Lou Tartaglia told BioWorld Today. One type is "pretty adipose-like" – essentially, a white fat cell running a different gene expression program. The other looks the same, but is descended from a different cell lineage developmentally. Irisin appears to work on the former type of cell, expressing brown fat-like gene expression programs in white fat cells. The hormone did not appear to have major effects on existing brown fat cells, presumably because they are already running the gene expression program that irisin would induce.

Ember, which got its official start last December with a $34 million Series A financing from Third Rock Ventures LLC, has an exclusive license to irisin, though the work now published in Nature was funded by academic grants, not through the company.

Ember is developing anti-obesity therapeutics based on irisin, as well as potential diabetes drugs that are also based on work out of Spiegelman's lab. (See BioWorld Today, July 22, 2010, and Dec. 15, 2011.)

Tartaglia said that Ember's management hopes to be ready for an investigational new drug application filing some time in 2014, but did not want to narrow down the possible date any more than that – partly because the company plans to run preclinical studies in primates as well as in rodents, and finding the best primate model can take time.

"Brown fat is very different in different mammals," he said, and although "it's good to do initial studies in the rodent to get a sense of what's going on," the best chances for success come from picking a good primate model and making sure an approach has good efficacy there, as well as in rodents. Although in at least one respect, irisin is impressively similar in mice and the primate homo sapiens: while the DNA sequences of the two species are 85 percent identical on the average, for irisin they are 100 percent identical.