Signaling and Physiology in Hematological Research, INSERM, UMR1231, Université Bourgogne Franche-Comté, Dijon, 21000, France.
LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, Dijon, 21000, France.
Nat Commun. 2019 Jan 31;10(1):523. doi: 10.1038/s41467-018-08228-0.
Despite recent in vivo data demonstrating that high-fat diet (HFD)-induced obesity leads to major perturbations in murine hematopoietic stem cells (HSC), the direct role of a HFD is not yet completely understood. Here, we investigate the direct impact of a short-term HFD on HSC and hematopoiesis in C57BL/6J mice compared with standard diet-fed mice. We detect a loss of half of the most primitive HSC in the bone marrow (BM) cells of HFD-fed mice, which exhibit lower hematopoietic reconstitution potential after transplantation. Impaired maintenance of HSC is due to reduced dormancy after HFD feeding. We discover that a HFD disrupts the TGF-β receptor within lipid rafts, associated to impaired Smad2/3-dependent TGF-β signaling, as the main molecular mechanism of action. Finally, injecting HFD-fed mice with recombinant TGF-β1 avoids the loss of HSC and alteration of the BM's ability to recover, underscoring the fact that a HFD affects TGF-β signaling on HSC.
尽管最近的体内数据表明高脂肪饮食（HFD）诱导的肥胖会导致小鼠造血干细胞（HSC）的重大紊乱，但 HFD 的直接作用尚未完全了解。在这里，我们研究了与标准饮食喂养的小鼠相比，短期 HFD 对 C57BL/6J 小鼠 HSC 和造血的直接影响。我们发现 HFD 喂养的小鼠骨髓（BM）细胞中最原始的 HSC 丢失了一半，其移植后的造血重建潜力较低。HSC 维持能力受损是由于 HFD 喂养后休眠减少所致。我们发现 HFD 破坏了脂筏内的 TGF-β 受体，与 Smad2/3 依赖的 TGF-β 信号传导受损有关，这是主要的作用机制。最后，向 HFD 喂养的小鼠注射重组 TGF-β1 可避免 HSC 的丢失和 BM 恢复能力的改变，这强调了 HFD 会影响 HSC 上的 TGF-β 信号。
