Scientists Uncover a Hidden “Backup Heater” in Fat That Burns Calories and Boosts Metabolism
Groundbreaking research reveals how peroxisomes in brown fat act as a secondary heat source, opening new avenues for tackling obesity and metabolic diseases.
October 9, 2025 – In a landmark study that could reshape our understanding of metabolism, scientists at Washington University School of Medicine in St. Louis have discovered a hidden "backup heater" within brown fat tissue. This system, driven by tiny cellular structures called peroxisomes, enables the body to burn energy and generate heat independently of traditional mechanisms, even without exercise.
The findings, published in Nature, point to novel strategies for combating metabolic conditions like obesity and insulin resistance by enhancing the body's innate calorie-burning processes.
The Hidden Power of Peroxisomes
Brown fat is unique in its ability to convert calories from food into heat, unlike white fat, which simply stores energy. Until now, this heat production was primarily attributed to mitochondria and a specific protein (UCP1). However, researchers observed that mice lacking UCP1 could still generate heat, hinting at an alternative pathway.
The team, led by senior author Dr. Irfan Lodhi, identified peroxisomes as this alternative heat source. When exposed to cold, these structures multiply inside brown fat cells. This response was even more pronounced in mice whose mitochondrial heat production was impaired, suggesting peroxisomes act as a compensatory "backup" system.
The ACOX2 Protein: Key to Heat Production
The study pinpointed a protein called acyl-CoA oxidase 2 (ACOX2) as the crucial driver of this process. ACOX2 enables peroxisomes to break down specific fatty acids, releasing energy as heat.
Using a custom-developed fluorescent heat sensor and infrared imaging, the researchers confirmed that brown fat cells became hotter when ACOX2 was active. Conversely, mice genetically engineered to lack ACOX2 in their brown fat were less cold-tolerant, showed poorer insulin sensitivity, and gained more weight on a high-fat diet.
In contrast, mice with elevated ACOX2 levels demonstrated increased heat production, better cold tolerance, and improved metabolic health, even when consuming a high-fat diet.
Future Implications for Human Health
The fatty acids metabolized by ACOX2 are not only produced by the body but are also found in dairy products and human breast milk and are synthesized by certain gut bacteria.
"This raises the possibility that a dietary intervention—such as a specific food, probiotic, or nutraceutical—could boost this heat-production pathway and its beneficial effects," said Dr. Lodhi.
While the studies were conducted in mice, the pathway is believed to be relevant to humans. Observational studies have previously found that individuals with higher levels of these key fatty acids tend to have lower body mass indices.
The research team is now exploring potential dietary interventions and drug compounds that could safely activate ACOX2 in humans, with the long-term goal of developing new treatments for weight management and metabolic health.
This work was supported by the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.