Hematopoietic stem cell-derived adipocytes suppress leptin production, and attenuate ovariectomy-induced inhibition of physical activity and insulin sensitivity in female mice.

Abstract

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.