Researchers at Weill Cornell Medicine have discovered that ordinary fat cells in obese animals can be triggered to burn stored energy and produce substantial heat, according to a new preclinical study published in Nature Metabolism. The findings suggest a potential new approach to weight loss that could complement existing therapies while avoiding common side effects.
The study focused on white adipocytes, the fat cells that make up the majority of body fat. The team found that high levels of fatty acids, in combination with an enzyme called AAC, can activate a process that converts stored fat directly into heat, increasing overall energy expenditure. In obese mice, this process led to measurable increases in body temperature—an effect that, if replicated over time, could result in significant weight loss.
“There is still much to explore, but this approach could be both effective and safe,” said Shannon Reilly, assistant professor of metabolic health at Weill Cornell Medicine and senior author of the study. “Unlike current weight-loss medications, which reduce appetite but often cause digestive side effects, this method could work alongside existing treatments at lower doses, minimizing unwanted reactions.”
How Fat Cells Burn Energy
For decades, scientists have sought ways to reduce fat by converting it into heat. Most cells use mitochondria—tiny oxygen-powered engines—to turn sugars and fats into ATP, the energy currency of the cell. While ATP production naturally generates some heat, a process called “uncoupling” allows mitochondria to burn fat solely for heat.
Brown adipocytes, a specialized type of fat cell, naturally use this mechanism to maintain body temperature and protect against obesity-related diseases such as diabetes and heart disease. However, brown fat is scarce in adults, especially in those with obesity, making it an impractical target for weight-loss therapies. Attempts to stimulate uncoupling across the entire body have also been dangerous. For example, the drug 2,4-dinitrophenol, once available over-the-counter in the U.S., caused fatal overheating and was banned in 1938. Stimulants like amphetamines carry similar risks.
Turning White Fat into Heat
The Weill Cornell team explored whether uncoupling could be induced specifically in white adipocytes, which are abundant in obesity. By simulating warmer environmental conditions for mice—analogous to human physiology—they were able to detect heat production in white fat cells, which had previously been underestimated.
Researchers focused on lipolysis, the natural process in which white adipocytes release stored fat. They found that this fat release triggers uncoupling in mitochondria when fatty acids interact with AAC, an enzyme similar to the uncoupling protein found in brown fat. Previously, the mechanism behind uncoupling in white adipocytes was unknown, and many scientists believed it could not contribute meaningfully to energy expenditure.
By activating this pathway in obese mice and controlling for heat from other sources, the team observed a clear rise in body temperature—demonstrating that white fat cells can inherently convert fat into heat.
Future Directions
Reilly and her colleagues now aim to develop methods to selectively enhance this uncoupling in white adipocytes. “The goal is to induce a small, targeted increase in heat production within fat cells,” she said. “Over time, this could provide a safe and effective way to support weight loss.”
