Fat cells play pivotal role in uridine and glucose regulations

Annie Zhang

During times of fasting, fat cells actually help the body regulate the metabolism, according to a recent study by UT Southwestern Medical Center.

Fat cells help regulate glucose metabolism through uridine, a building block for RNA and DNA that is responsible for many biochemical pathways, according to Yingfeng Deng, assistant professor of internal medicine.

“Our studies uncovered a direct link between uridine and energy expenditure, and we also found that fat cells are critical regulators of uridine,” Deng said. 

According to Philipp Scherer, senior author of the study, liver and fat cells alternate in uridine production responsibilities. 

In the fed state, a healthy liver will shut down glucose production and produce uridine, but in the fasted state, the fat cells will produce uridine and allow the liver to focus on glucose production. 

“This fasting-induced increase in uridine causes a drop in body temperature and reduces the metabolic rate,” Scherer said. “It is well established that rodents’ and humans’ body temperatures (decrease) while fasting and increase after a meal. It seems that uridine is a driving force for these changes.”

According to Deng, the maintenance of energy balance is crucial for survival, and thermoregulation, or the ability of an organism to keep its body temperature within certain ranges, serves as the basic strategy for energy metabolism. 

“Since the body temperature is always higher than the surroundings, the larger the difference in temperature, the higher the energy expenditure to maintain (body temperature),” Deng said. “As an organ for energy storage, fat cells have been extensively studied for how they can generate heat to defend body temperature during cold exposure.”

However, the exact role of fat cells when body temperature drops remained largely unknown. 

“It was believed that some biological function, similar to an air conditioning unit, could exist for mammals’ thermoregulation, which can efficiently lower body temperature when needed,” Deng said. “Our study identified such a role for uridine, which lowers body temperature through its (breakdown of molecules). Combining our discovery and other groups’ (discoveries), we can now redefine the role of fat cells in thermoregulation as they can initiate temperature change in both directions.“

The study has important implications for diseases such as diabetes, she said. 

Deng’s team proposed that diabetes is a result of disrupted uridine balance, as the regulation of uridine involves the liver, fat and the digestive system. 

“Uridine is a harmless but important building block that can be removed through the digestive system when in excess,” Scherer said. “Can we prompt fat cells to chronically overproduce uridine, thereby prompting a ‘futile’ biosynthetic reaction that consumes calories (without) any negative consequences? We’re (proposing) to follow the conceptual approach of using inhibitors to ‘waste’ uridine.”

Deng said she believes that understanding the disruption in this condition will lead to a cure for diabetes.

“In the future, (we want) to understand how uridine (balance) regulation is altered in diabetes, and how the uridine effects on glucose metabolism observed in rodents translate to humans,” Deng said.