In mouse brown fat, one mitochondrial carrier responds to the clock, cold and dietary fat
University of Copenhagen researchers report in Science that cold raised the mitochondrial carrier SLC25A34 90-fold in mouse brown fat after 24 hours. Because the body clock and dietary fat also control it, the lead author sees a possible new obesity-drug lever in work done so far in mice.
The Scientist · Science desk
What happened
- The carrier surfaced in a search of large mouse brown-fat datasets for proteins that respond to both the clock and cold, alongside the heat-producing protein UCP1.
- Mice lacking specific regulators revealed three controls: REV-ERB alpha holds the gene off during sleep, cold lifts that brake at any hour, and fat switches it on via PPAR alpha.
- Fasting and insulin, the body's signals for burning fat and for storing it, both raised SLC25A34 levels.
- The authors say their biochemical and metabolic data support a model in which the carrier moves oxaloacetate into mitochondria.
Why it matters
- Who has to decide decision Because REV-ERB alpha shuts the gene off during sleep, a drug aimed at this carrier would likely act differently by time of day. Dosing time would be a design question from the start.
- What it limits constraint With storage and burning signals both raising the carrier, a drug that boosts it cannot be assumed to steer fat cells only toward burning.
- What's now possible capability A named cargo, oxaloacetate, gives other labs a specific transport step to test or block when probing brown fat's heat-making fat cycle.
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That 90-fold rise starts from almost nothing [6][7]. In mice kept comfortably warm, brown fat holds less SLC25A34 than almost any other organ [6]. After a day in the cold, it holds more than any tissue in the body [7]. The thing the fold change doesn't tell you is how much carrier the tissue makes in absolute terms. The ranking helps: cold moves brown fat from near the bottom of the body's tissues to the top [6][7].
The genetic work is the best part of the design. Mice engineered to lack specific regulatory proteins let the team see which signal stopped moving the gene when a given controller was missing [8]. In the picture that emerged, the clock sets a default schedule and the other inputs override it on demand [8][17]. When cold or a fatty meal creates a need the clock did not anticipate, the authors wrote, "REV-ERB repression is rapidly overridden and PPARs are activated by lipolytic signals to boost SLC25A34 levels" [17]. Once the demand is met, the daily rhythm returns [17]. The authors had framed the puzzle this way: "How thermogenic fat can seamlessly achieve both rhythmic continuity and acute responsiveness is a fundamental question of energy homeostasis that has remained unknown" [16].
The fasting-and-insulin result looks contradictory until you see what active brown fat does with fat. It builds new fat molecules and then burns them, a loop that makes heat and clears fat and sugar from the blood [13]. In that tissue, storing and burning are two halves of one cycle, and the carrier's proposed job is to keep the cycle turning [13][14].
Without the carrier, brown fat cells burned less fuel [15]. The report does not give the size of that drop, and it describes no SLC25A34 measurements in human tissue. The human observation it includes concerns brown fat's daily rhythm: "In mice and humans, BAT metabolic activity begins to increase just before waking, peaks late in the waking period, and then declines to its lowest point during sleep," the authors wrote [4].
"We usually think of the body clock, the response to temperature, and the response to food as separate systems," said Gerhart-Hines, who leads the work at Copenhagen's NNF Center for Basic Metabolic Research and is a co-corresponding author of the Science paper [3][1][2]. He sees a clinical opening where those systems meet [19]. "A mitochondrial transporter that is tuned by the 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," he said [19].
I think the regulatory map is strong mouse physiology [18], and the drug idea is a reasonable hypothesis one step further out. The reported test removes the carrier and watches fuel use fall [15]. A therapy aimed at boosting energy expenditure would have to push the carrier the other way, in human fat [20][15].
What to watch
- Whether raising SLC25A34 activity in mice increases energy expenditure or limits weight gain on a fatty diet, the direction a drug would need.
- Measurements of SLC25A34 in human brown fat, and whether it rises and falls with the daily rhythm the authors describe in people.
- Independent transport assays confirming oxaloacetate as the carrier's cargo.
Clarity's read
What the record supports and how the coverage leans. The claims behind it follow.
Reality
- Evidence55
- Adoption
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- Hype gap+25
- Incentives
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- [1]
Researchers at the University of Copenhagen's NNF Center for Basic Metabolic Research (CBMR), headed by associate professor Zach Gerhart-Hines, found that SLC25A34, a little-studied protein in the mitochondria of fat cells, acts as a switch connecting the body clock, temperature and diet to how fat cells store and spend energy.
- [2]
Gerhart-Hines is co-corresponding author of the paper in Science titled "Mitochondrial carrier SLC25A34 links clock, diet, and temperature control of adipocyte lipid cycling."
- [3]
"We usually think of the body clock, the response to temperature, and the response to food as separate systems," said Gerhart-Hines.
- [4]
The authors wrote: "In mice and humans, BAT metabolic activity begins to increase just before waking, peaks late in the waking period, and then declines to its lowest point during sleep."
- [5]
The researchers searched large datasets for proteins in mouse brown fat that respond to both the clock and the cold, identifying UCP1, the best-known heat-producing protein, and SLC25A34, a related transporter with an unknown job.
- [6]
In mice kept comfortably warm, brown fat contains less SLC25A34 than almost any other organ.
- [7]
After 24 hours in the cold, SLC25A34 levels in mouse brown fat rose 90-fold, making brown fat the tissue with the most SLC25A34 in the body.
- [8]
Studying mice engineered to lack specific regulatory proteins, the team found three separate controls on the Slc25a34 gene, each answering to a different signal.
- [9]
The clock protein REV-ERB alpha keeps Slc25a34 switched off during sleep and releases it before waking.
- [10]
Cold lifts the REV-ERB brake on Slc25a34 at any hour, overriding the schedule when extra heat is needed.
- [11]
Fat, from the tissue's own stores or the diet, switches the Slc25a34 gene on through PPAR alpha.
- [12]
Both fasting, which promotes using fat, and insulin, which promotes building fat, increase SLC25A34 levels, so signals for burning and storing fat run through the same transporter.
- [13]
Active brown fat builds new fat molecules to then burn them, a cycle that generates heat and clears fat and sugar from the blood.
- [14]
SLC25A34 appears to keep the cycle turning by carrying oxaloacetate back into mitochondria; the authors wrote: "Our biochemical and metabolic data support a functional model in which SLC25A34 transports oxaloacetate into mitochondria."
- [15]
Without the transporter, brown fat cells burned less fuel.
- [16]
The authors wrote: "How thermogenic fat can seamlessly achieve both rhythmic continuity and acute responsiveness is a fundamental question of energy homeostasis that has remained unknown."
- [17]
The authors wrote that when animals face an unanticipated need for energy expenditure such as cold or a lipid-rich meal, "REV-ERB repression is rapidly overridden and PPARs are activated by lipolytic signals to boost SLC25A34 levels"; when the energy demand is met, the REV-ERB-mediated rhythm of Slc25a34 is reestablished.
- [18]
The regulatory experiments described (the dataset search in mouse brown fat, cold exposure, and mice engineered to lack regulatory proteins) were done in mice.
- [19]
"A mitochondrial transporter that is tuned by the 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."
- [20]
According to GEN, the findings could point to new approaches to therapeutically boost energy expenditure in metabolic disease.
Sources
2 independent publishers whose own reporting we read for this story.
- genengnews.comMitochondrial Transporter Connects Body Clock and Diet to Fat Burning
1 article · October 1, 2026
- neurosciencenews.comHow the Body Clock and Cold Team Up to Burn Fat
1 article · October 3, 2026
Topics and entities
Topics
- Obesity and metabolic disease
- Mitochondrial transporters
- Circadian metabolism
- Brown adipose tissue
Entities
- Science
- Iuliia Karavaeva
- Zach Gerhart-Hines
- University of Copenhagen
- NNF Center for Basic Metabolic Research