A hunger protein reverses anorexia symptoms in mice

An appetite-stimulating protein can reverse anorexia in mice.

Mice with lack of appetite and weight loss — symptoms similar to people with anorexia — that were genetically tweaked to secrete a protein called ACBP ate more food and weighed more than anorexic animals with an ACBP deficit, researchers report August 14 in Science Translational Medicine. The finding points to a potential treatment target for people with the eating disorder.

“Anorexia is a whole brain and body illness” that is difficult to treat, says psychiatrist and neuroscientist Rachel Ross, who wasn’t involved with the new work. “One of the major challenges is that the brain of a person with anorexia is directly fighting against their body.” While the body screams for food, the brain prioritizes the need to restrict weight (SN: 7/26/13).

Globally, around 1 percent of women and 0.2 percent of men develop the disorder. Roughly just a third of those people fully recover. Yet, no drugs are available; treatment typically involves medical care to stabilize weight and therapy to mend patients’ relationships with food. Some cancer patients can also develop a similar disorder called cancer cachexia, which comes from an impaired metabolism, that is similarly tough to treat (SN: 7/30/24).

“Anything that has the potential to provide some sort of mechanism that would be useful for creating a new therapeutic is huge,” says Ross, of Albert Einstein College of Medicine and Montefiore Health System in New York City. And although there’s no guarantee the results will apply to people, the new findings suggest that ACBP, a protein that helps turn on parts of the brain that arouse appetite, may have that potential.

Previous work has shown that ACBP levels tend to be lower in patients with more severe anorexia. In the new work, Hui Chen of Sorbonne University in Paris and colleagues used chronic stress or chemotherapy to induce anorexia in mice, robbing the animals of appetite and causing weight loss. The animals were genetically modified to release ACBP when exposed to biotin, a form of vitamin B. As their ACBP levels went up, animals stopped losing weight and had better appetites, the team found.

Compared with mice lacking the protein, the bodies of biotin-exposed mice had more lean body weight and fat. Daily ACBP injections given to non-genetically engineered mice also stopped the animals from becoming anorexic.

What the results mean for people is unclear. The team took plasma samples from patients hospitalized with severe anorexia and found those with lower ACBP levels than average were more likely to relapse a month later than patients with higher levels. But there was enough variability among patients to make it difficult to know who might benefit from receiving a theoretical ACBP-based drug, says Tim Moran, a neuroscientist at Johns Hopkins School of Medicine. “It would be interesting to see a longer follow-up period,” to know if patients who had low ACBP levels but didn’t relapse after a month might go back to restricting food just a few months later.

Anorexia’s strong psychiatric component makes it unlikely that any drug targeting ACBP alone would be a silver bullet treatment. Nor is it known how ACBP sparks an increase in appetite. Figuring that out could help researchers pinpoint which patients such drugs might help the most, whether it’s those with cancer cachexia or those with anorexia whose bodies are malnourished.

Still, Ross says, “even if this protein isn’t the slam dunk treatment for anorexia we definitely need, it does provide [evidence of] an important new connection” between the body and the brain.