Katiraei Saeed, Hoving Lisa R, van Beek Lianne, Mohamedhoesein Sharida, Carlotti Françoise, van Diepen Janna A, Rensen Patrick C N, Netea Mihai G, Willems van Dijk Ko, Berbée Jimmy F P, van Harmelen Vanessa
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
PLoS One. 2017 Apr 26;12(4):e0175524. doi: 10.1371/journal.pone.0175524. eCollection 2017.
Experimental bone marrow transplantation (BMT) in mice is commonly used to assess the role of immune cell-specific genes in various pathophysiological settings. The application of BMT in obesity research is hampered by the significant reduction in high-fat diet (HFD)-induced obesity. We set out to characterize metabolic tissues that may be affected by the BMT procedure and impair the HFD-induced response. Male C57BL/6 mice underwent syngeneic BMT using lethal irradiation. After a recovery period of 8 weeks they were fed a low-fat diet (LFD) or HFD for 16 weeks. HFD-induced obesity was reduced in mice after BMT as compared to HFD-fed control mice, characterized by both a reduced fat (-33%; p<0.01) and lean (-11%; p<0.01) mass, while food intake and energy expenditure were unaffected. As compared to control mice, BMT-treated mice had a reduced mature adipocyte volume (approx. -45%; p<0.05) and reduced numbers of preadipocytes (-38%; p<0.05) and macrophages (-62%; p<0.05) in subcutaneous, gonadal and visceral white adipose tissue. In BMT-treated mice, pancreas weight (-46%; p<0.01) was disproportionally decreased. This was associated with reduced plasma insulin (-68%; p<0.05) and C-peptide (-37%; p<0.01) levels and a delayed glucose clearance in BMT-treated mice on HFD as compared to control mice. In conclusion, the reduction in HFD-induced obesity after BMT in mice is at least partly due to alterations in the adipose tissue cell pool composition as well as to a decreased pancreatic secretion of the anabolic hormone insulin. These effects should be considered when interpreting results of experimental BMT in metabolic studies.
小鼠实验性骨髓移植（BMT）常用于评估免疫细胞特异性基因在各种病理生理环境中的作用。BMT在肥胖研究中的应用受到高脂饮食（HFD）诱导的肥胖显著降低的阻碍。我们着手表征可能受BMT程序影响并损害HFD诱导反应的代谢组织。雄性C57BL/6小鼠接受致死性照射后进行同基因BMT。在8周的恢复期后，它们被喂食低脂饮食（LFD）或HFD 16周。与喂食HFD的对照小鼠相比，BMT后小鼠的HFD诱导肥胖减少，其特征是脂肪量（-33%；p<0.01）和瘦体重（-11%；p<0.01）均减少，而食物摄入量和能量消耗未受影响。与对照小鼠相比，BMT处理的小鼠皮下、性腺和内脏白色脂肪组织中的成熟脂肪细胞体积减小（约-45%；p<0.05），前脂肪细胞数量减少（-38%；p<0.05），巨噬细胞数量减少（-62%；p<0.05）。在BMT处理的小鼠中，胰腺重量不成比例地降低（-46%；p<0.01）。这与血浆胰岛素（-68%；p<0.05）和C肽（-37%；p<0.01）水平降低以及与对照小鼠相比，BMT处理的HFD小鼠的葡萄糖清除延迟有关。总之，小鼠BMT后HFD诱导的肥胖减少至少部分是由于脂肪组织细胞池组成的改变以及合成代谢激素胰岛素的胰腺分泌减少。在解释代谢研究中实验性BMT的结果时应考虑这些影响。
