Without a system of protein interactions to govern when organisms like humans feel hungry and compelled to eat, there’s no telling how people would manage their nutrition. However, the human body does have a system to regulate hunger, and new research from the Research Unit Neurobiology of Diabetes led by Dr. Paul Pfluger and at the Institute for Diabetes and Obesity led by Prof. Dr. Matthias Tschöp has led to the discovery of a new player.
The enzyme they discovered, called HDAC5, is considered to be a “genetic switch” in the pathway to leptin-resistance and satiety. Leptin, a hormone secreted by fat tissue to communicate the fat storage is at capacity, leads to the feeling of being “full.” When someone feels full, generally they stop eating, and their body runs on a “negative energy balance,” meaning they obtain energy from fat stores instead of incoming food.
However, just like the presence of leptin hormone reduces food intake, the feeling of hunger returns just as soon as leptin stops being produced. As soon as fat stores being to deplete again, they produce less and less leptin, which induces the feeling of hunger and the inclination to eat again.
It works like this. HDAC5 activates a transcription factor called STAT3 by deacetylating it, enabling STAT3 to bind and activate a leptin receptor. In turn, STAT3 activates genes that prompt satiety. With HDAC5, leptin, STAT3, or any other component of this pathway missing, the feeling of being full does not exist, and there’s no chemical reaction to tell the body to stop eating.
In their new study published in
Nature Communications, Pfluger and Tschop identified missing HDAC5 as a potential explanation for people who struggle with weight gain.
"In addition to the essential changes in diet and exercise behavior, in the future the individual components of the leptin effect could be potential drug targets to support the weight loss process,” Pfluger said.
Source:
German Research Center for Environmental Health
