Department of Orthopaedic Surgery, University of Toledo Health Sciences Campus, Toledo, OH 43614, USA.
Bone. 2012 Feb;50(2):546-52. doi: 10.1016/j.bone.2011.06.016. Epub 2011 Jun 24.
Fat occupies a significant portion of bone cavity however its function is largely unknown. Marrow fat expands during aging and in conditions which affect energy metabolism, indicating that fat in bone is under similar regulatory mechanisms as other fat depots. On the other hand, its location may determine specific functions in the maintenance of the environment for bone remodeling and hematopoiesis. We have demonstrated that marrow fat has a distinctive phenotype, which resembles both, white and brown adipose tissue (WAT and BAT, respectively). Marrow adipocytes express gene markers of brown adipocytes at levels characteristic for the BAT, including transcription factor Prdm16, and regulators of thermogenesis such as deiodinase 2 (Dio2) and PGC1α. The levels of expression of BAT-specific gene markers are decreased in bone of 24 mo old C57BL/6 and in diabetic yellow agouti A(vy)/a mice implicating functional changes of marrow fat occurring with aging and diabetes. Administration of antidiabetic TZD rosiglitazone, which sensitizes cells to insulin and increases adipocyte metabolic functions, significantly increased both, BAT (UCP1, PGC1α, Dio2, β3AR, Prdm16, and FoxC2) and WAT (adiponectin and leptin) gene expression in marrow of normoglycemic C57BL/6 mice, but failed to increase the expression of BAT, but not WAT, gene markers in diabetic mice. In conclusion, the metabolic phenotype of marrow fat combines both BAT and WAT characteristics. Decrease in BAT-like characteristics with aging and diabetes may contribute to the negative changes in the marrow environment supporting bone remodeling and hematopoiesis.
脂肪占据了骨腔的很大一部分，但其功能在很大程度上尚不清楚。骨髓脂肪在衰老和影响能量代谢的情况下会扩张，这表明骨内脂肪受到与其他脂肪储存相似的调节机制的影响。另一方面，其位置可能决定了其在维持骨重塑和造血环境方面的特定功能。我们已经证明，骨髓脂肪具有独特的表型，它类似于白色和棕色脂肪组织（分别为 WAT 和 BAT）。骨髓脂肪细胞表达棕色脂肪细胞的基因标志物，其水平特征与 BAT 相似，包括转录因子 Prdm16 以及产热调节剂如脱碘酶 2（Dio2）和 PGC1α。24 个月大的 C57BL/6 小鼠和糖尿病黄色 agouti A(vy)/a 小鼠的骨中 BAT 特异性基因标志物的表达水平降低，这表明随着衰老和糖尿病的发生，骨髓脂肪的功能发生了变化。给予抗糖尿病 TZD 罗格列酮（可使细胞对胰岛素敏感并增加脂肪细胞代谢功能）可显著增加正常血糖 C57BL/6 小鼠骨髓中的 BAT（UCP1、PGC1α、Dio2、β3AR、Prdm16 和 FoxC2）和 WAT（脂联素和瘦素）基因表达，但未能增加糖尿病小鼠的 BAT 基因标志物表达，而不是 WAT。总之，骨髓脂肪的代谢表型结合了 BAT 和 WAT 的特征。随着衰老和糖尿病，BAT 样特征的减少可能导致支持骨重塑和造血的骨髓环境的负面变化。
