Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, Level 3 WCHRE, 176 Furlong Road, St. Albans, VIC, 3021, Australia.
Department of Medicine-Western Health, Melbourne Medical School, The University of Melbourne, St. Albans, VIC, Australia.
Curr Osteoporos Rep. 2018 Apr;16(2):130-137. doi: 10.1007/s11914-018-0427-y.
Bone marrow fat expresses mixed characteristics, which could correspond to white, brown, and beige types of fat. Marrow fat could act as either energy storing and adipokine secreting white fat or as a source of energy for hematopoiesis and bone metabolism, thus acting as brown fat. However, there is also a negative interaction between marrow fat and other elements of the bone marrow milieu, which is known as lipotoxicity. In this review, we will describe the good and bad roles of marrow fat in the bone, while focusing on the specific components of the negative effect of marrow fat on bone metabolism.
Lipotoxicity in the bone is exerted by bone marrow fat through the secretion of adipokines and free fatty acids (FFA) (predominantly palmitate). High levels of FFA found in the bone marrow of aged and osteoporotic bone are associated with decreased osteoblastogenesis and bone formation, decreased hematopoiesis, and increased osteoclastogenesis. In addition, FFA such as palmitate and stearate induce apoptosis and dysfunctional autophagy in the osteoblasts, thus affecting their differentiation and function. Regulation of marrow fat could become a therapeutic target for osteoporosis. Inhibition of the synthesis of FFA by marrow fat could facilitate osteoblastogenesis and bone formation while affecting osteoclastogenesis. However, further studies testing this hypothesis are still required.
骨髓脂肪具有混合特征,可能对应于白色、棕色和米色脂肪。骨髓脂肪可以作为储存能量和分泌脂联素的白色脂肪,也可以作为造血和骨代谢的能量来源,从而发挥棕色脂肪的作用。然而,骨髓脂肪与骨髓环境中的其他元素之间也存在负相互作用,即脂毒性。在这篇综述中,我们将描述骨髓脂肪在骨骼中的有益和有害作用,同时重点介绍骨髓脂肪对骨代谢的负面影响的具体成分。
骨髓脂肪通过分泌脂联素和游离脂肪酸(FFA)(主要是棕榈酸)在骨骼中发挥脂毒性作用。在老年和骨质疏松骨骼的骨髓中发现的高水平 FFA 与成骨细胞形成和骨形成减少、造血减少和破骨细胞形成增加有关。此外,FFA 如棕榈酸和硬脂酸诱导成骨细胞凋亡和功能障碍性自噬,从而影响其分化和功能。调节骨髓脂肪可能成为骨质疏松症的治疗靶点。通过抑制骨髓脂肪中 FFA 的合成,可以促进成骨细胞形成和骨形成,同时影响破骨细胞形成。然而,仍需要进一步的研究来验证这一假设。