PDF(Pubmed)
Abstract：
UNASSIGNED: Unlike white adipose tissue depots, bone marrow adipose tissue (BMAT) expands during caloric restriction (CR). Although mechanisms for BMAT expansion remain unclear, prior research suggested an intermediary role for increased circulating glucocorticoids.
UNASSIGNED: In this study, we utilized a recently described mouse model (BMAd-Cre) to exclusively target bone marrow adipocytes (BMAds) for elimination of the glucocorticoid receptor (GR) (i.e. Nr3c1) whilst maintaining GR expression in other adipose depots.
UNASSIGNED: Mice lacking GR in BMAds (BMAd-Nr3c1 -/-) and control mice (BMAd-Nr3c1 +/+) were fed ad libitum or placed on a 30% CR diet for six weeks. On a normal chow diet, tibiae of female BMAd-Nr3c1-/- mice had slightly elevated proximal trabecular metaphyseal bone volume fraction and thickness. Both control and BMAd-Nr3c1-/- mice had increased circulating glucocorticoids and elevated numbers of BMAds in the proximal tibia following CR. However, no significant differences in trabecular and cortical bone were observed, and quantification with osmium tetroxide and μCT revealed no difference in BMAT accumulation between control or BMAd-Nr3c1 -/- mice. Differences in BMAd size were not observed between BMAd-Nr3c1-/- and control mice. Interestingly, BMAd-Nr3c1-/- mice had decreased circulating white blood cell counts 4 h into the light cycle.
UNASSIGNED: In conclusion, our data suggest that eliminating GR from BMAd has minor effects on bone and hematopoiesis, and does not impair BMAT accumulation during CR.
UNASSIGNED: In this study, we utilized a recently described mouse model (BMAd-Cre) to exclusively target bone marrow adipocytes (BMAds) for elimination of the glucocorticoid receptor (GR) (i.e. Nr3c1) whilst maintaining GR expression in other adipose depots.
UNASSIGNED: Mice lacking GR in BMAds (BMAd-Nr3c1 -/-) and control mice (BMAd-Nr3c1 +/+) were fed ad libitum or placed on a 30% CR diet for six weeks. On a normal chow diet, tibiae of female BMAd-Nr3c1-/- mice had slightly elevated proximal trabecular metaphyseal bone volume fraction and thickness. Both control and BMAd-Nr3c1-/- mice had increased circulating glucocorticoids and elevated numbers of BMAds in the proximal tibia following CR. However, no significant differences in trabecular and cortical bone were observed, and quantification with osmium tetroxide and μCT revealed no difference in BMAT accumulation between control or BMAd-Nr3c1 -/- mice. Differences in BMAd size were not observed between BMAd-Nr3c1-/- and control mice. Interestingly, BMAd-Nr3c1-/- mice had decreased circulating white blood cell counts 4 h into the light cycle.
UNASSIGNED: In conclusion, our data suggest that eliminating GR from BMAd has minor effects on bone and hematopoiesis, and does not impair BMAT accumulation during CR.
摘要：
■与白色脂肪组织库不同，骨髓脂肪组织（BMAT）在热量限制（CR）期间膨胀。尽管BMAT扩展的机制尚不清楚，先前的研究表明，循环糖皮质激素的增加具有中介作用。
■在这项研究中，我们利用最近描述的小鼠模型（BMAd-Cre）专门靶向骨髓脂肪细胞（BMAds），以消除糖皮质激素受体（GR）（即Nr3c1），同时维持GR在其他脂肪储库中的表达。
■在BMAd中缺乏GR的小鼠(BMAd-Nr3c1-/-)和对照小鼠(BMAd-Nr3c1+/+)随意饲喂或置于30%CR饮食中6周。在正常的饮食中，雌性BMAd-Nr3c1-/-小鼠的胫骨近端骨小梁干meta下骨的体积分数和厚度略有升高。对照和BMAd-Nr3c1-/-小鼠在CR后胫骨近端循环糖皮质激素增加和BMAd数量增加。然而,小梁骨和皮质骨没有观察到显著差异，用四氧化锇和μCT定量显示对照或BMAd-Nr3c1-/-小鼠之间的BMAT积累没有差异。在BMAd-Nr3cl-/-和对照小鼠之间未观察到BMAd大小的差异。有趣的是,BMAd-Nr3c1-/-小鼠进入光周期4小时后循环白细胞计数降低。
■总而言之，我们的数据表明，从BMAd中消除GR对骨骼和造血功能影响较小，并且不损害CR期间的BMAT积累。
■在这项研究中，我们利用最近描述的小鼠模型（BMAd-Cre）专门靶向骨髓脂肪细胞（BMAds），以消除糖皮质激素受体（GR）（即Nr3c1），同时维持GR在其他脂肪储库中的表达。
■在BMAd中缺乏GR的小鼠(BMAd-Nr3c1-/-)和对照小鼠(BMAd-Nr3c1+/+)随意饲喂或置于30%CR饮食中6周。在正常的饮食中，雌性BMAd-Nr3c1-/-小鼠的胫骨近端骨小梁干meta下骨的体积分数和厚度略有升高。对照和BMAd-Nr3c1-/-小鼠在CR后胫骨近端循环糖皮质激素增加和BMAd数量增加。然而,小梁骨和皮质骨没有观察到显著差异，用四氧化锇和μCT定量显示对照或BMAd-Nr3c1-/-小鼠之间的BMAT积累没有差异。在BMAd-Nr3cl-/-和对照小鼠之间未观察到BMAd大小的差异。有趣的是,BMAd-Nr3c1-/-小鼠进入光周期4小时后循环白细胞计数降低。
■总而言之，我们的数据表明，从BMAd中消除GR对骨骼和造血功能影响较小，并且不损害CR期间的BMAT积累。
