Bistable regulation of adipocyte heterogeneity governs thermogenesis.

Cold exposure reduces IL-1β in brown adipose tissue, enabling H6PD degradation and converting BA-L to BA-H cells, which enhances UCP1-dependent thermogenesis in mice.

• Why it matters: Age-related declines in thermogenesis and cold sensitivity are linked to brown adipocyte heterogeneity, but how immune and neural signals stabilize distinct BA states was unclear.
• What they did: The study showed that IL-1β from neutrophils and macrophages stabilizes H6PD protein to sustain active glucocorticoids, activating GR (Nr3c1) and increasing Rgs2 to suppress UCP1; cold exposure reversed this, and BA-specific inducible Nr3c1 deletion locked BA-H.
• The result: In aged mice, elevated IL-1β locked a low BA-H/BA-L ratio and cold intolerance; suppressing GR restored the BA-H/BA-L ratio, resumed thermogenesis, and increased energy expenditure.

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