A Wnt/β-catenin signaling driven adipocyte population required for beiging and glucose homeostasis

ABSTRACT Wnt/β-catenin signaling has been well established as a potent inhibitor of adipogenesis. Here, we identified a population of Wnt/β-catenin signaling driven adipocytes in embryonic and adult mouse fat depots. We showed that Wnt/β-catenin signaling activation in these cells relies on AKT/mTOR signaling intracellularly and is essential for cell survival. Such adipocytes are distinct from classical ones in transcriptomic and genomic signatures and can be induced from various sources of mesenchymal stromal cells including human cells. Using genetic lineage-tracing and targeted cell ablation mouse models, these adipocytes were shown to not only convert into beige adipocytes directly but be also required for beige fat recruitment under thermal challenge, demonstrating a central role in initiating adaptive thermogenesis. Mice bearing targeted ablation of these adipocytes exhibited glucose intolerance, while mice receiving exogenously supplied such cells manifested enhanced glucose utilization. Our studies uncover a unique adipocyte population in regulating beiging and systemic glucose homeostasis.