Called leptin, a new study has revealed some of the molecular machinery behind its functioning, and shown how the loss of a key protein can drive insatiable appetites and obesity in mice.
Leptin is a hormone produced by fat cells that carries out a range of functions in the body, chief among them being the regulation of appetite. It does by communicating with the brain region called the hypothalamus to let the person know they've had enough to eat, but this relationship can break down in people with obesity.
While the higher amount of fat cells in the body means higher levels of leptin, this doesn't necessarily mean better suppression of appetite. The leptin signals can fail to have the desired effect in these cases, with the leptin receptors in the brain not activating as they should, leading the person to overeat and continue to gain weight. This is known as leptin resistance.
Scientists aren't exactly sure why a high-fat diet or overeating causes leptin resistance, but a team from the Okinawa Institute of Science and Technology has shed new light on the issue via experiments in mice. These rodents were engineered to be lacking a protein found in neurons in the forebrain, where the hypothalamus is found, called XRN1.
At the age of six weeks, mice lacking the XRN1 protein began to quickly gain weight and at the age of 12 weeks, had become obese, with fat accumulating in their adipose tissue and in the liver. Observing the behavior of these mice along with a control group, those without XRN1 were found to be eating almost twice the amount each day.
"This finding was really surprising," says study author Dr. Shohei Takaoka. "When we first knocked out XRN1 in the brain, we didn't know exactly what we would find, but this drastic increase in appetite was very unexpected."