New research has revealed that a molecule called uridine plays a role in appetite regulation. This discovery could pave the way for potential new targets to control appetite and obesity.
In recent years, researchers have been identifying new pathways and molecules that regulate body weight and glucose (sugar) levels in humans. These can help determine targets for novel therapies to combat the increasing burden of diseases such as obesity and diabetes, and may also be applicable to PWS.
Studying UDP and Appetite In Mice
Recently, scientists at the Max Planck institute in Germany studied the relationship between a molecule called uridine di-phosphate (UDP) and appetite in laboratory mice. They discovered that injecting UDP in the brains of mice activated appetite inducing (orexigenic) brain cells and made the mice eat significantly more compared to mice that had normal levels of UDP. Interestingly, the researchers also found increased levels of UDP in the hypothalamus of mice that were obese due to over-feeding, as well as in genetically obese mice. The hypothalamus is a small but very important part of the brain that regulates, among other things, appetite and body temperature, and its function is thought to be disrupted in PWS.
UDP and Uridine
Uridine diphosphate is a key factor in the process of storing carbohydrates (glycogen synthesis) and is made from a molecule called uridine, which is a building block for RNA and thus a very essential molecule in our bodies. Uridine is required for the growth and survival of cells in our bodies, therefore, like glucose, the level of uridine in blood is very tightly regulated. As UDP is made from uridine, its levels in the brain are directly dependent upon the level of uridine in blood.
Fasting and Feeding Regulate Uridine
In a recently published study aimed at understanding the mechanisms behind the tight regulation of uridine, scientists discovered that blood uridine may act as a “hunger signal.” They found that in the fasted stated, blood uridine levels go up and this is closely associated with a drop in core body temperature. Increased blood uridine levels would imply increased UDP in the brain and an increased appetite. After eating, the uridine levels fell back down due to rapid clearance of uridine by the liver and an associated increase in insulin sensitivity, which they discovered was dependent on leptin, a “satiety hormone” which acts on brain cells to decrease appetite. The researchers also showed that fat cells, also known as adipocytes, are the primary source of uridine during fasting.
Thus, although these studies are very new, they point to a potentially important role of uridine in regulating body temperature and appetite. Additional studies will be needed to determine if uridine and UDP play a role in the hyperphagia associated with PWS. However, these exciting new studies offer potential new targets to control appetite and obesity.
