Inducible Brown Adipose Tissue, or Beige Fat, Is Anabolic for the Skeleton
Inducible Brown Adipose Tissue, or Beige Fat, Is Anabolic for the Skeleton
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DOI：
10.1210/en.2012-2162
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发表时间：
2013-08-01
期刊：
影响因子：
4.8
通讯作者：
Lecka-Czernik, Beata
中科院分区：
文献类型：
--
作者：
Rahman, Sima;Lu, Yalin;Lecka-Czernik, Beata
众所周知，胰岛素抵抗和2型糖尿病与骨折增加有关，棕色脂肪组织（BAT）抵消了许多（如果不是全部的话）与2型糖尿病相关的症状。通过使用FoxC2(AD)（+/Tg）小鼠（一种成熟的诱导BAT或米色脂肪的模型），我们提供的数据将米色脂肪的有益作用扩展到对骨骼的积极作用。FoxC2(AD)（+/Tg）小鼠瘦且胰岛素敏感，由于骨形成增加与高骨转换相关，具有高骨量。诱导型BAT与内皮成骨细胞的激活有关，而骨细胞编码硬化蛋白的Sost转录物表达减少，Rankl表达升高。从叉头盒c2 （FOXC2）诱导的米色脂肪细胞中收集的条件培养基（CM）激活了成骨细胞表型，并增加了受体细胞中磷酸化akt和β -catenin的水平。在骨细胞中，同样的培养基降低了Sost的表达。用抗无翼相关MMTV整合位点10b （WNT10b）和胰岛素样生长因子结合蛋白2 （IGFBP2）的抗体对CM进行免疫消耗，导致成骨前活性丧失，磷酸化akt和β -catenin水平的升高丧失。相反，来自过表达IGFBP2或WNT10b的细胞的CM可以恢复受体细胞的成骨细胞活性。综上所述，米色脂肪分泌的内分泌/旁分泌活性对骨骼有益。
It is known that insulin resistance and type 2 diabetes mellitus are associated with increased fractures and that brown adipose tissue (BAT) counteracts many if not all of the symptoms associated with type 2 diabetes. By the use of FoxC2(AD)(+/Tg) mice, a well-established model for induction of BAT, or beige fat, we present data extending the beneficial action of beige fat to also include a positive effect on bone. FoxC2(AD)(+/Tg) mice are lean and insulin-sensitive and have high bone mass due to increased bone formation associated with high bone turnover. Inducible BAT is linked to activation of endosteal osteoblasts whereas osteocytes have decreased expression of the Sost transcript encoding sclerostin and elevated expression of Rankl. Conditioned media (CM) collected from forkhead box c2 (FOXC2)-induced beige adipocytes activated the osteoblast phenotype and increased levels of phospho-AKT and beta-catenin in recipient cells. In osteocytes, the same media decreased Sost expression. Immunodepletion of CM with antibodies against wingless related MMTV integration site 10b (WNT10b) and insulin-like growth factor binding protein 2 (IGFBP2) resulted in the loss of pro-osteoblastic activity, and the loss of increase in the levels of phospho-AKT and beta-catenin. Conversely, CM derived from cells overexpressing IGFBP2 or WNT10b restored osteoblastic activity in recipient cells. In conclusion, beige fat secretes endocrine/paracrine activity that is beneficial for the skeleton.