Ordinary fat cells, long considered simply storage depots for energy, may hold a key to unlocking a new approach to weight loss. A preclinical study by researchers at Weill Cornell Medicine suggests that these cells – known as white adipocytes – can be induced to burn energy and generate heat, potentially offering a novel therapeutic strategy for obesity.
The findings, published on , in Nature Metabolism, demonstrate that when white adipocytes are exposed to high levels of fatty acids, in the presence of an enzyme called AAC (ATP/ADP carrier), a process of “uncoupling” is triggered. This uncoupling allows the cells to produce heat instead of storing energy as fat. This process was observed in obese mice, raising the possibility of significant weight loss over time.
“There is still a lot of research to do, but in principle this approach to treating obesity might be very effective and safe,” said Dr. Shannon Reilly, study senior author and Assistant Professor of Metabolic Health in Medicine at Weill Cornell Medicine. “Current weight-loss medications work by reducing hunger but sometimes have unpleasant digestive side effects. This new approach complements these existing therapies and thus could potentially be used in conjunction with lower doses to minimize unwanted side effects.”
The concept of harnessing heat production to combat obesity isn’t new. For decades, scientists have known that brown adipose tissue (BAT) is specialized for thermogenesis – the creation of heat. Unlike white fat, which stores energy, brown fat actively burns calories to maintain body temperature. However, brown fat is relatively scarce in adults, limiting its potential as a weight-loss target. Previous attempts to activate brown fat have also proven challenging.
earlier attempts to induce uncoupling throughout the body using drugs like 2,4-dinitrophenol proved dangerous, with potentially fatal overheating as a side effect. Other stimulants, while effective, carried risks of addiction and adverse effects. The Weill Cornell Medicine study focuses on a more targeted approach: inducing uncoupling specifically within white adipocytes, which are abundant in obesity, making them an attractive therapeutic target.
A key element of the study’s success was the experimental setup. Previous research suggesting that only brown adipocytes produce heat was potentially skewed by the temperature at which the mice were housed. Researchers found that standard room temperature for humans doesn’t accurately reflect the thermal environment for a smaller animal like a mouse. By housing the mice at – a temperature more analogous to “room temperature” for mice – the researchers were able to more accurately observe metabolic processes.
Under these warmer conditions, the team observed heat production in white adipocytes during a natural process called lipolysis, where the cells mobilize their fat stores to release energy. They discovered that this lipolysis triggered uncoupling within the mitochondria of the white adipocytes, driven by the interaction of fatty acids with the AAC enzyme. AAC is an evolutionary relative of the uncoupling protein found in brown adipocytes, but its role in heat production had not previously been demonstrated in mammals.
“Uncoupling in white adipocytes has been observed in prior studies, but the mechanism was unknown,” Dr. Reilly explained. “The consensus in the field had been that it couldn’t be a relevant source of energy consumption or heat production.”
To test this, the researchers activated lipolysis in obese mice, increasing fatty acids and inducing uncoupling via AAC. They carefully controlled the experiment to minimize any contribution from brown fat or muscle activity, confirming that the observed rise in body temperature was directly attributable to the uncoupling process in white adipocytes. This suggests that, over time, this energy-burning effect could lead to measurable weight loss.
The study’s findings challenge the long-held belief that white fat cells are incapable of significant heat production. They demonstrate that white fat cells possess an inherent ability to convert fat into heat, even without the specialized features of brown adipocytes.
Dr. Reilly and her team are now focused on identifying a safe and effective method to selectively enhance this uncoupling ability within white adipocytes. “The idea would be to cause a small increase in heat production, just in the fat cells, which over time could be a very effective and safe way to promote weight loss,” she said.
While the research is still in its early stages, it offers a promising new avenue for obesity treatment, potentially complementing existing therapies and minimizing unwanted side effects. Further research will be crucial to translate these findings into clinical applications and determine the long-term safety and efficacy of this approach.
