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Distinct signaling requirements underlie beige fat recruitment in development versus adulthood


In adult mammals, beige fat is recruited in response to environmental cold in order to generate heat (thermogenesis) and maintain a constant body temperature. It is also transiently and physiologically induced in postnatal animals; however, little is known about how this process is regulated. Here, we use light sheet microscopy, high throughput sequencing, and metabolic assays to show that although the spatiotemporal kinetics of recruitment are very similar in young and adult mice, distinct regulatory signals prevail at each time point. Systemic adrenergic signaling or environmental cold stimulus is required only for beiging in adult, but not postnatal animals. In contrast, postnatal beiging depends on tissue- and cell-intrinsic pathways such as type 2 cytokines and adipocyte B-cell lymphoma 6 (BCL6) respectively. In adults, BCL6 is required for neither transdifferentiation of naïve adipocytes, nor reactivation of dormant cells. Together, our findings reveal an unexpected distinction between beige fat regulation in postnatal and adult animals, thereby introducing a previously-unappreciated temporal dimension to the study of the beiging process.

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