An older adult outdoors in winter. Editorial illustration.
Brown fat helps mammals warm up without shivering. In older mice, a new study in Nature found that an inflammatory signal made it harder for this tissue to respond to cold. Blocking a hormone receptor partially restored that response and increased energy use in the animals. Samples of human brown fat showed a similar pattern of two key proteins, giving researchers a place to look for the same mechanism in people.
Evidence level Early Research. The team tested the mechanism and intervention in mice and compared molecular markers in human tissue.
How brown fat turns fuel into heat
Brown adipose tissue contains many mitochondria, the structures that extract energy from sugars and fats. A mitochondrial protein called uncoupling protein 1, or UCP1, lets some of that energy dissipate as heat. Sympathetic nerves help activate this process when temperatures fall.
Brown fat cells can shift between states with higher and lower UCP1 levels. That flexibility lets the tissue increase heat production as the need arises. The study found that older mice made that shift more slowly. In one experiment, after three days of cold exposure, about 51% of their brown fat cells were in the high-UCP1 state, compared with about 90% in younger mice. Brown fat is one part of temperature regulation, which also depends on processes such as shivering and controlling heat loss through the skin.
How inflammation dampened the cold response
The researchers used fluorescent markers to track the two cell states. Neutrophils and macrophages, two kinds of immune cells, released interleukin-1 beta (IL-1β). The signal helped a protein called H6PD persist in nearby brown fat cells. H6PD supports the local production of active glucocorticoids, hormones that act through the glucocorticoid receptor.
When that receptor is active, cells make more RGS2. This protein weakens the internal signal that normally raises UCP1 in response to cold. In younger mice, sympathetic nerves released noradrenaline during cold exposure, reducing local IL-1β and allowing more brown fat cells to enter the high-UCP1 state. Older mice had more inflammatory signalling in the tissue, and their brown fat was slower to switch.
What changed when researchers blocked the receptor
After one week of treatment with the glucocorticoid receptor blocker mifepristone, about 33% of brown fat cells in treated older mice entered the high-UCP1 state after one day in the cold, compared with about 11% in controls. The treated mice maintained a higher body temperature during a cold challenge. Separate measurements also showed higher oxygen consumption and energy expenditure.
The change in energy use matters because brown fat draws on glucose and fatty acids to produce heat. The experiments link cold tolerance to how the tissue uses fuel. They did not track long-term metabolic health or lifespan.
What the human samples add
Brown fat sampled from above the collarbone showed largely separate populations of cells marked by UCP1 or H6PD, similar to the pattern in mice. The tissue comparison did not test whether local inflammation drives cold sensitivity in older people or whether blocking the receptor would help them maintain body temperature.
The next step is to establish whether the pathway changes with human age and whether changing it in brown fat improves cold tolerance without disrupting glucocorticoid signalling elsewhere. The mouse experiments identify a possible contributor to cold sensitivity and give researchers a way to test that possibility.
Related reading on how longevity interventions changed metabolism in mice.
Original research
Song A, Wang Y, Wang G, et al. Bistable regulation of adipocyte heterogeneity governs thermogenesis. Nature, November 11, 2026.