Breakthrough Study Reprograms Obese Fat Cells to Boost Metabolism

Researchers at Weill Cornell Medicine have identified a new way to make ordinary white fat cells burn energy and produce heat, a discovery that could open the door to safer obesity treatments. The preclinical study, published in Nature Metabolism, shows that this mechanism works even in obese mice and may lead to meaningful weight loss over time.

Most fat in the human body consists of white adipocytes, which primarily store excess energy. In contrast, brown fat cells are specialized to burn fat and generate heat through a process called mitochondrial “uncoupling.” While activating brown fat has long been considered a potential obesity therapy, these cells are relatively scarce and less active in adults. Past attempts to stimulate widespread uncoupling in the body have been dangerous. The weight-loss drug 2,4-dinitrophenol, for example, was banned after causing fatal overheating.

In the new study, senior author Dr. Shannon Reilly and her team explored whether uncoupling could be safely triggered directly within white fat cells. They found that during lipolysis—the breakdown of stored fat—released fatty acids interact with an enzyme called AAC (adenine nucleotide translocase). AAC then promotes mitochondrial uncoupling, allowing fat to be burned purely for heat instead of being converted into ATP, the cell’s energy currency.

Importantly, when researchers activated this pathway in obese mice housed under conditions mimicking human metabolism, the animals showed clear increases in body temperature even when brown fat and muscle activity were minimized. This indicates that white fat cells themselves can meaningfully contribute to energy expenditure.

The findings suggest that selectively boosting heat production in white adipocytes could complement existing appetite-suppressing drugs and potentially reduce their side effects, offering a promising new strategy for long-term weight management.

REFERENCE: Ahmadian, M., et al. (2026). Fatty acids promote uncoupled respiration via ATP/ADP carriers in white adipocytes. Nature Metabolism. DOI: 10.1038/s42255-026-01467-2. https://www.nature.com/articles/s42255-026-01467-2.