Brown fat, or adipose tissue, is responsible for generating heat to maintain body temperature. Research has shown its presence and activity to be beneficial in the context of aging, in that the presence of more brown adipose improves long-term health. However, like all tissues, brown adipose tissue becomes dysfunctional with age. Here, researchers investigate what appears to be an important mechanisms in this process, in which brown fat adipocyte cells and macrophage cells of the innate immune system interact in ways that provoke inflammation and dysfunction.
Loss of brown adipose tissue (BAT) activity observed during ageing, obesity, and living at thermoneutrality is associated with lipid accumulation, fibrosis, and tissue inflammation in BAT. The mechanisms that promote this degenerative process of BAT remain largely enigmatic. Here, we show that an imbalance between sympathetic activation and mitochondrial energy handling causes BAT degeneration, which leads to impaired energy expenditure and systemic metabolic disturbances.
Mechanistically, we demonstrate that brown adipocytes secrete adenosine triphosphate (ATP) in response to imbalanced thermogenic activation, which activates the P2X4 and P2X7 receptors of BAT-resident macrophages. Notably, mice lacking activity of these purinergic receptors in myeloid cells are protected against BAT inflammation, thermogenic dysfunction, and systemic metabolic disturbances under conditions of imbalanced BAT activation, thermoneutrality, or overnutrition. These results highlight the relevance of extracellular ATP released by brown adipocytes as a paracrine signal for myeloid cells to initiate BAT degeneration.
Link: https://doi.org/10.1038/s44319-025-00642-y
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