Obesity: a protein to regulate appetite?

Obesity is a complex disease. It corresponds to an imbalance between energy intake and expenditure, the causes of which are sometimes unknown or poorly understood. According to Japanese researchers, it could be linked to a protein present in our brain. In their research, published on the specialized site iSciencethey explain that the XRN1 protein is involved in the functioning of appetite and metabolism.

Twice as much power

“We still know very little about how appetite or metabolism are regulated by communication between the brain and parts of the body, such as the pancreas, liver, and fatty tissue.“, explains Dr. Akiko Yanagiya, one of the authors of this study. With his colleagues, he worked on the XRN1 protein: it is made in the forebrain, an area which includes the hypothalamus, which releases some of involved in regulating body temperature, thirst and hunger. To better understand its role, Japanese scientists performed experiments on mice. Some were modified to prevent them from producing the protein XRN1. After six weeks , they found that the mice without XRN1 quickly began to gain weight. They became obese at the age of 12 weeks. The researchers then looked at the amounts consumed by the mice: they noticed that the mice without XRN1 ate nearly twice as much each day as the control mice. “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.“, says Dr. Shohei Takaoka, co-author.

What increases the appetite of mice?

Blood samples were taken from the rodents to observe the level of various hormones related to satiety and appetite. In the case of leptin, a hunger-related hormone, levels were abnormally high in mice without XRN1, which in principle must keep the mice from feeling hungry. But unlike control mice, mice without XRN1 did not respond to the presence of leptin, this phenomenon is called leptin resistance. They were also insulin resistant: as the experiment progressed, their glucose and insulin levels increased. In humans, insulin resistance can lead to diabetes. “We believe glucose and insulin levels increased due to the lack of response to leptin.”says Dr. Yanagiya.

A surprising use of energy

Japanese scientists wanted to understand the energy expenditure of mice. They were all placed in a special cage that measured the amount of oxygen used to calculate their metabolic rate. In six-week-old mice, the scientists found no difference in energy expenditure. But they made an unexpected discovery: Mice without XRN1 primarily used carbs for energy, while control mice could switch between burning carbs at night, when they were most active, and burning fat during sleep. day, when they were less active. According to the researchers, this means that the absence of the protein prevents mice from properly using fat for their energy expenditure, and leads to weight gain. They plan to continue their research to better understand the role of the XRN1 protein, and eventually develop a targeted treatment for obesity.