Brown fat has long been celebrated as the body’s built-in furnace, a specialized tissue that burns fuel to generate heat rather than storing energy as white fat does. Its activity follows a familiar daily pattern: it ebbs during sleep and surges in the hours before waking, when the body prepares to face the day. Yet life rarely sticks to a schedule. A cold morning, a skipped meal, or an unexpected feast all place demands on metabolism that the circadian clock never anticipated. For decades, researchers have puzzled over how the body maintains a fixed energetic timetable while still improvising when circumstances change. A new study from the University of Copenhagen, published in the journal Science, now identifies a molecular switch that appears to resolve this paradox, and its discovery could reshape how scientists think about treating obesity and diabetes.
The switch is a protein called SLC25A34, a little-studied transporter embedded in the membranes of mitochondria, the power plants inside fat cells. Researchers at the university’s Novo Nordisk Foundation Center for Basic Metabolic Research, known as CBMR, found that this single protein is tuned simultaneously by three forces: the time of day, the ambient temperature, and what the animal eats. In doing so, it connects the body’s 24-hour clock to the fat cell’s decisions about storing and spending energy. According to corresponding author Associate Professor Zach Gerhart-Hines, the finding challenges the conventional view that these are separate systems. A mitochondrial transporter that responds to clock, cold, and diet, he notes, raises the possibility of therapies that shift when and how the body burns fuel, a fundamentally different lever from today’s obesity and diabetes treatments.
The discovery began as a data-mining exercise. The team searched large datasets for proteins in mouse brown fat that respond to both the circadian clock and to cold exposure, hoping to find candidates that might bridge the two signals. Only two proteins passed every test. One was UCP1, the famous uncoupling protein that converts fuel directly into heat and has been the centerpiece of brown fat research for decades. The other was SLC25A34, a related mitochondrial transporter whose function had never been established. Under comfortable warm conditions, brown fat contains less SLC25A34 than almost any other organ in the mouse. But after just 24 hours in the cold, levels of the protein rose an astonishing 90-fold, transforming brown fat into the tissue with the highest abundance of SLC25A34 in the entire body. That dramatic swing suggested the protein plays a central role in the tissue’s adaptive response.
To understand how the gene encoding the protein, Slc25a34, is controlled, the researchers studied mice engineered to lack specific regulatory proteins. What emerged was a remarkably layered control system with three separate inputs, each answering to a different signal. A clock protein called REV-ERBα keeps the gene switched off during sleep and releases the brake before waking, aligning the transporter’s production with the animal’s daily rhythm. Cold exposure lifts that brake at any hour of the day, overriding the circadian schedule whenever extra heat is urgently needed. And fat itself, whether mobilized from the tissue’s own stores or delivered by the diet, switches the gene on through a third protein, PPARα, a well-known sensor of fatty acids. In effect, the gene listens to the clock, the thermostat, and the pantry all at once.
One of the study’s most intriguing findings is a seeming contradiction. Both fasting, which pushes the body to burn fat, and insulin, the hormone that drives fat storage, increase SLC25A34 levels. Signals for burning fat and building fat, two processes usually treated as opposites, converge on the same transporter. The explanation lies in a quirk of brown fat biology: when the tissue is activated, it does not simply burn pre-existing fat. Instead, it actively builds new fat molecules and then burns them in a continuous cycle. This lipid cycling generates heat as a byproduct and, in the process, clears fat and sugar from the bloodstream, which helps explain why active brown fat is associated with better metabolic health. SLC25A34 appears to keep this cycle turning by carrying a molecule called oxaloacetate back into the mitochondria, replenishing a critical intermediate needed to keep fat synthesis running.
The functional importance of the transporter became clear when the researchers removed it. Brown fat cells lacking SLC25A34 burned less fuel, and in living mice the tissue’s fat-burning response was significantly weaker. The team has not yet demonstrated directly that the transporter carries oxaloacetate, nor have they determined what losing it means for long-term health, so important questions remain open. Still, the evidence points to SLC25A34 as a necessary component of the fat-building-and-burning engine that makes brown fat such a powerful metabolic organ. The work also hints at broader roles: the protein is highly expressed in the heart and has been implicated in brain and liver metabolism, though its function in those organs remains a mystery.
Human relevance is suggested by two lines of evidence, both of which come with caveats. In brown fat cells obtained from human donors, silencing the transporter reduced fuel burning in cells from three of four individuals, indicating that the mechanism is not unique to mice. More strikingly, across 24 clinical studies, people with more SLC25A34 in the white fat beneath their skin tended to be leaner and metabolically healthier. The researchers are careful to stress that this is an association, not proof of cause. It is possible that higher levels of the transporter contribute to leanness, or that leaner, healthier people simply express more of it. Distinguishing between these possibilities will require further study, but the correlation adds weight to the idea that this transporter matters for human metabolism.
The implications for medicine are considerable. Current treatments for obesity and diabetes generally aim to reduce energy intake or alter how the body handles glucose and lipids. A therapy that instead shifts when and how the body burns fuel, by modulating a transporter that integrates circadian, thermal, and dietary signals, would operate on an entirely different axis. Timing of energy expenditure, rather than its total amount alone, could become a therapeutic target. The concept resonates with a growing body of research on circadian metabolism, which has shown that the same meal can have different metabolic consequences depending on when it is eaten. A molecular handle on that timing, situated inside the mitochondria of fat cells, offers a concrete biochemical entry point.
Much remains to be learned. The Copenhagen team, working with collaborators at institutions including the University of Southern Denmark, the University of Pennsylvania, Harvard Medical School, the Broad Institute, and many others across Europe and North America, has only begun to map the transporter’s reach. First author Iuliia Karavaeva of CBMR emphasizes that many mitochondrial transporters still have no known function, and that SLC25A34 turned out to be needed both for building fat and for burning it, a dual role nobody expected. As she puts it, researchers are only scratching the surface. Whether the same clock-temperature-diet integration operates in human brown fat, whether the transporter can be safely targeted with drugs, and what it does in the heart, brain, and liver are questions for the next chapter. For now, the study provides a vivid example of how a single, previously overlooked protein can sit at the crossroads of some of biology’s most fundamental rhythms, turning the body’s furnace up, down, and on schedule.
Subject of Research: Mitochondrial transporter SLC25A34 in brown fat links circadian clock, temperature, and diet to lipid cycling
Article Title: A molecular switch syncs fat-burning to the body clock, our diet and the temperature around us
Article References: A molecular switch syncs fat-burning to the body clock, our diet and the temperature around us. (n.d.). Original publication
Image Credits: AI Generated
DOI: Not provided
Keywords: brown fat, SLC25A34, mitochondria, circadian clock, metabolism, thermogenesis, obesity, diabetes, lipid cycling, UCP1, PPARα, REV-ERBα
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Daisy Hatcher. (October 3, 2026). Molecular switch in brown fat syncs fat-burning with body clock, diet and cold. Scienmag. https://scienmag.com/molecular-switch-in-brown-fat-syncs-fat-burning-with-body-clock-diet-and-cold/
Daisy Hatcher. “Molecular switch in brown fat syncs fat-burning with body clock, diet and cold.” Scienmag, 3 October 2026, https://scienmag.com/molecular-switch-in-brown-fat-syncs-fat-burning-with-body-clock-diet-and-cold/. Accessed 3 October 2026.
Daisy Hatcher. “Molecular switch in brown fat syncs fat-burning with body clock, diet and cold.” Scienmag. October 3, 2026. https://scienmag.com/molecular-switch-in-brown-fat-syncs-fat-burning-with-body-clock-diet-and-cold/
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Tags: body clock and temperature influencebrown fatbrown vs white fatcircadian clockcircadian rhythmdiabetesdiet and cold adaptationenergy expenditurefat metabolism regulationlipid cyclingmetabolic flexibilitymetabolismmitochondriamitochondria in fat cellsmolecular switchobesityobesity and diabetes treatmentPPARαREV-ERBαSLC25A34SLC25A34 proteinthermogenesisUCP1
