Photo Caption: Researchers found the during times of stress, like fasting or being exposed to cold temperatures, the human body can activate a secondary system to burn fat and generate heat.
By Kat Procyk
A seasoned survivalist in a cold environment knows that staying warm is crucial as the temperature begins to plummet.
Normally, a survivalist’s body relies on cytosolic lipolysis—the breakdown of stored fat into free fatty acids (FFAs) and glycerol within the cell’s cytoplasm—to generate energy for heat. However, in the tundra, the survivalist’s body could activate a backup system recently discovered by researchers at the University of Pittsburgh School of Medicine.
Both labs of Babak Razani, professor of medicine and director of the Center for Immunometabolism, and Matthew Steinhauser, associate professor of medicine, investigated lysosomal lipolysis, a lesser-known process for the breakdown of fats that happens in a cell’s lysosomes, and how it plays a role when a body faces stress, like frigid temperatures or fasting. Both senior authors published their studies in early 2025, Razani in the Journal of Clinical Investigation and Steinhauser in Nature Communications.
“Lysosomes are like the cell’s recycling center,” Razani said. “They’re basically small organelles that are filled with different types of enzymes and acids that can degrade any nutrient, including fats, and reuse them as new building blocks.”
In cytosolic lipolysis, adipose triglyceride lipase (ATGL) is the first and most essential enzyme to kick off the process by breaking down triglycerides into diglycerides and releasing the first FFA. It’s the classic, faster route for the body to survive under stressful conditions. Hormone-sensitive lipase (HSL) and monoacylglycerol lipase (MAGL) then continue the breakdown to release more FFAs and glycerol.
In lysosomal lipolysis, however, both Razani and Steinhauser found that the process uses an enzyme called lysosomal acid lipase (LIPA). In Steinhauser’s study, which focused on fasting only, his lab found that a group of proteins called MiT/TFE supports lysosomal lipolysis by activating the genes that are involved in lysosomal function, including the one responsible for making LIPA.
“This novel discovery in fat metabolism highlights the collaborative environment at Pitt,” Steinhauser said. “Even though we weren’t working directly together, we trusted and learned from each other as we investigated this process separately.”
Razani’s study further explored how this fat-burning system may affect obesity and metabolic diseases and found that lysosomal lipolysis is important for preventing fat cell enlargement during obesity.
“What we learned is that when this process doesn’t work, fat cells swell up with too much fat,” Razani said. “This can worsen obesity and contribute to other complications of the disease, like insulin resistance.”