A new study by Yale researchers has uncovered the physiological mechanism controlling appetite.

The study discovered that neural pathways of an area of the brain governing appetite are under constant flux according to hormonal changes, and may account for why obesity treatments are largely unsuccessful. The study revealed the way Leptin, a hormone produced in fat, causes changes in brain function to control appetite. While this new information will not directly lead to new obesity treatments, this new insight into neuron function may help researches better understand appetite and obesity.

A section of the brain called the hypothalamus releases a variety of hormones controlling bodily functions such as reproduction, growth hormone, behavioral aspects of sexual behavior and appetite. Leptin is involved in the sensation of hunger and inhibits cells that stimulate appetite and galvanizes cells that suppress appetite, said study co-author Dr. Jeffrey Friedman of the Howard Hughes Medical Institute at Rockefeller University in New York, who discovered Leptin in 1994. Mice engineered with a complete lack of Leptin have uncontrolled appetite and become extremely obese.

“Basically, we’ve been interested in understanding the connectivity of brain center for food intake,” said Dr. Tamas Horvath, senior author and Yale School of Medicine associate professor of neurobiology, obstetrics and gynecology. “The connectivity is not hard wired, and is constantly changing based on the metabolic state — When you need to eat, the synaptology of the cells that make you eat are supporting increased firing of those neurons, and then, when you’ve eaten enough, you have changes in that synaptology.”

Friedman said the mechanism of memory, considered “higher” brain function, is known to involve the same plasticity, or changing neural pathways. Horvath said the findings raise the question of the connection between appetite and metabolism, and more complicated brain function.

“[These findings] raise the question of whether the hormones’ effects may affect plasticity of higher brain sections,” Horvath said. “The question is, is it possible to envision that cognition is altered when you have an altered metabolic position.”

Though an absence of Leptin has been shown to cause obesity in lab mice, a lack of the hormone or faulty Leptin receptors is not usually the cause of obesity in humans, making the disease very hard to treat, said Yale School of Medicine associate professor of obstetrics and gynecology Dr. Sabrina Diano.

“It has been shown that humans who completely lack Leptin are not as many as one would like to think, because then, everyone could get an injection of Leptin,” Diano said. “There are very few cases within the obese population of people lacking Leptin. There are many other causes of obesity. That’s why it’s so hard to cure.”

However, Horvath said while Leptin itself may not be helpful in directly treating obesity, knowledge of brain synaptology may be an asset to treating the disease.

“We are hypothesizing that actually, the plasticity is probably not a very important component in treating who are obese, because this plasticity is impaired, so it would not be able to adjust itself,” Horvath said. “But understanding the mechanism of the plasticity may help the development of new drugs against obesity.”

Horvath also said the research may also be applicable to other diseases — Alzheimer’s disease, for example, involves the failing plasticity of brain function.

Future studies will involve research into other means of changing brain architecture, leading to possible treatments for obesity.

Other researchers on the study were Dr. Marya Shanabrough, research associate in the Yale School of Medicine department of obstetrics and gynecology, and Dr. Shirly Pinto, Dr. Aaron G. Roseberry, Dr. Hongyan Liu, and Dr. Xiaoli Cai of the Howard Hughes Medical Institute at Rockefeller University.