Libby Andrew E, Sullivan Timothy M, Maltzahn Joanne K, Jackman Matthew R, Gavin Kathleen M, MacLean Paul S, Kohrt Wendy M, Majka Susan M, Klemm Dwight J
Division of Endocrinology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Cardiovascular Pulmonary Research Laboratory, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Adipocyte. 2025 Dec;14(1):2536813. doi: 10.1080/21623945.2025.2536813. Epub 2025 Aug 4.
A subpopulation of adipocytes in mice and humans is produced from haematopoietic stem cells rather than mesenchymal progenitors; the source of conventional white and brown/beige adipocytes. The abundance of these haematopoietic stem cell-derived adipocytes (HSCDAs) is elevated in female mice by ovariectomy (OVX) or oestrogen receptor alpha (ERα) knockdown, suggesting that they may be involved in the metabolic and inflammatory pathology that accompany the loss of oestrogen signalling. However, we previously demonstrated that ablation of HSCDAs elevated circulating leptin levels while suppressing physical activity and insulin sensitivity. Here, we tested the combined impact of OVX with and without HSCDA ablation. We discovered that HSCDA depletion plus OVX raised circulating leptin levels more than HSCDA depletion alone. Likewise, while HSCDA depletion or OVX alone inhibited physical activity and insulin responsiveness, their combination further suppressed these endpoints. Other physiologic endpoints were regulated by OVX alone. We conclude that HSCDAs play a role inthe maintenance of a subset of metabolic endpoints related to normal adipose tissue function, and their elevated production in models of female sex hormone suppression occurs to normalize these endpoints. The results highlight the ability of HSCDAs to target physical activity and insulin responsiveness, possibly by normalizing leptin production.
小鼠和人类脂肪细胞的一个亚群由造血干细胞产生，而非传统白色和棕色/米色脂肪细胞的来源——间充质祖细胞。卵巢切除术（OVX）或雌激素受体α（ERα）敲低会使雌性小鼠中这些造血干细胞衍生的脂肪细胞（HSCDA）数量增加，这表明它们可能参与了伴随雌激素信号缺失的代谢和炎症病理过程。然而，我们之前证明，去除HSCDA会提高循环瘦素水平，同时抑制身体活动和胰岛素敏感性。在此，我们测试了有无HSCDA消融的OVX的联合影响。我们发现，去除HSCDA加OVX比单独去除HSCDA更能提高循环瘦素水平。同样，虽然单独去除HSCDA或OVX会抑制身体活动和胰岛素反应性，但它们的联合作用会进一步抑制这些指标。其他生理指标仅受OVX调节。我们得出结论，HSCDA在维持与正常脂肪组织功能相关的一部分代谢指标中发挥作用，并且在雌性性激素抑制模型中其产量增加是为了使这些指标正常化。结果突出了HSCDA可能通过使瘦素产生正常化来靶向身体活动和胰岛素反应性的能力。
