Brown fat burns fuel to make heat, and this activity is controlled by the body clock: It drops during sleep and rises before waking. But a cold morning or a skipped meal makes demands the clock never planned for. How the body keeps to a fixed energy timetable while still improvising has long been a puzzle.
Researchers at the University of Copenhagen’s NNF Center for Basic Metabolic Research (CBMR) now show that SLC25A34, a little-studied protein in the mitochondria of fat cells, acts as a switch that connects the body clock, temperature and diet to how fat cells store and spend energy. The study was published in Science.
“We usually think of the body clock, the response to temperature and the response to food as separate systems. A mitochondrial transporter that is tuned by the⁰ time of day, the temperature and what we eat) raises the possibility of therapies that shift when and how the body burns fuel. That would be a different kind of lever from today’s obesity and diabetes treatments,” says corresponding author Zach Gerhart-Hines, an associate professor at CBMR.
Cold reveals an overlooked transporter
The researchers started their study by searching large datasets for proteins in mouse brown fat that respond to both the clock and the cold. Only two passed every test: UCP1, the best-known heat-producing protein, and SLC25A34, a related transporter whose job was unknown. In mice kept comfortably warm, brown fat contains less SLC25A34 than almost any other organ. But after 24 hours in the cold, its levels rose 90-fold, making brown fat the tissue with the most SLC25A34 in the body.
To work out how the Slc25a34 gene is controlled, the team studied mice engineered to lack particular regulatory proteins. They found three separate controls, each responding to a different signal. A clock protein, REV-ERBα, keeps the gene switched off during sleep and releases it before waking. Cold lifts this brake at any hour, overriding the schedule when extra heat is needed. And fat, from the tissue’s own stores or the diet, switches the Slc25a34 gene on through another protein, PPARα.
Opposing fat signals share a transporter
Seemingly paradoxically, both fasting, which promotes fat use, and insulin, the hormone that promotes fat storage, increase SLC25A34 levels. This means that signals for burning and storing fat run through the same transporter. Active brown fat builds new fat molecules and then burns them, a cycle that generates heat and clears fat and sugar from the blood.
SLC25A34 appears to keep the cycle turning by carrying a molecule called )oxaloacetate back into the mitochondria. Without the transporter, brown fat cells burned less fuel, and in mice, the tissue’s fat-burning response was significantly weaker. The team has yet to show directly that the transporter carries oxaloacetate or what losing it means for long-term health.
Human evidence leaves open questions
Silencing the transporter in brown fat cells from three of four human donors also reduced their fuel burning. Across 24 clinical studies, people with more SLC25A34 in the white fat beneath their skin tended to be leaner and 00s metabolically healthier. This is an association and does not prove cause.
“Many of these mitochondrial transporters still have no known function. This one turned out to be needed both for building fat and for burning it. And we are only scratching the surface: SLC25A34 is also highly expressed in the heart and is implicated in brain and liver metabolism, but what it does in those organs remains a mystery,” says Iuliia Karavaeva of CBMR, the study’s first author. https://medicalxpress.com/news/2026-09-molecular-syncs-fat-body-clock.html
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