Protein Acts as Sensor to Guard against Obesity and Diabetes

    Scientists in Australia have identified an internal sensor that helps fight obesity by instructing cells to burn their fat stores. The finding could play a major role in the fight against obesity and metabolic diseases, including type 2 diabetes.

    In the study (“IL-18 Production from the NLRP1 Inflammasome Prevents Obesity and Metabolic Syndrome”), published in Cell Metabolism, researchers showed a protein called NLRP1 is switched on when increased dietary energy (food) intake triggers the cell to become unstable. Activating the protein sets off a chain of events that instructs cells to use up their energy or fat stores to prevent excess fat accumulating.

    Seth Masters, Ph.D., from Melbourne’s Walter and Eliza Hall Institute, said NLRP1 was a biological sensor that could hold the key to developing new ways of treating obesity and type 2 diabetes.

    “The sensor is activated if it detects that the body’s energy intake is too high,” he explained. “When the sensor is activated, it tells cells to burn fat stores to prevent excess build up of fat. We showed that without NLRP1, fat stores continue to build up, especially with a high-energy diet, leading to obesity.”

    Dr. Masters noted that NLRP1 was more commonly known for its role in the immune system, adding that “it is becoming increasingly clear that immune signaling proteins also have an important role in regulating metabolism.”

    Andrew Murphy, Ph.D., of the Baker IDI Heart and Diabetes Institute, believes  the collaboration between two of Australia’s leading institutes in immunology and metabolism research provided new insights into obesity.

    “This study provides compelling evidence that the immune system is activated not only during infection, but also in response to the loss of metabolic ‘equilibrium’ associated with a high-energy diet,” he said. “In order to combat the world-wide obesity epidemic it is essential to understand the immune mechanisms the body uses to prevent obesity, insulin resistance and development of type 2 diabetes.”

    The key to NLRP1 and its anti-obesity effects is how it controls an important lipid-regulating hormone called interleukin-18 (IL-18), according to Dr. Murphy, who said that “We showed for the first time that NLRP1 is the key to IL-18 production, explaining how it acts to reduce obesity. Our long-term goal would be to develop a small molecule that activates the pathway to produce IL-18. In people who are obese, this would help the body to switch on this system and burn existing fat stores.”