Kyung Tae-Wook, Lee Ji-Eun, Phan Tien Van, Yu Rina, Choi Hye-Seon
Department of Biological Sciences (BK21 Program) and the Immunomodulation Research Center, University of Ulsan, Ulsan 680-749, Korea.
J Nutr. 2009 Mar;139(3):502-6. doi: 10.3945/jn.108.100032. Epub 2009 Jan 28.
Obesity induces a low-grade systemic chronic inflammatory condition for which macrophages are responsible. We hypothesized that obesity affects osteoclastogenesis by acting on bone marrow-derived macrophages (BMM). Male mice were fed a high-fat diet (45% of energy) or a standard diet (10% of energy) for 13 wk. We found that the density of the femurs of obese mice was significantly lower than that of the femurs of lean mice. Osteoclastogenesis was enhanced in the BMM from obese mice. Lower levels of interleukin (IL)-10 were generated by the BMM from obese mice than by those from lean mice upon stimulation of receptor activator of nuclear factor-kappaB ligand. Neutralization of IL-10 in the BMM from obese mice was not as effective in increasing osteoclast (OC) formation as that in those from lean mice. Exogenous IL-10 inhibited OC formation more strongly in the BMM from obese mice than those from lean mice. The elevated level of OC formation in the BMM from obese mice may thus be due to in part to the lower level of IL-10, a negative regulator of osteoclastogenesis. Our results suggest that obesity is associated with bone loss via enhanced osteoclastogenesis due to reduced IL-10 production by the BMM from obese mice.
肥胖会引发一种由巨噬细胞介导的低度全身性慢性炎症状态。我们推测肥胖通过作用于骨髓来源的巨噬细胞（BMM）影响破骨细胞生成。雄性小鼠分别喂食高脂饮食（能量的45%）或标准饮食（能量的10%），持续13周。我们发现肥胖小鼠股骨的密度显著低于瘦小鼠股骨的密度。肥胖小鼠的BMM中破骨细胞生成增强。在受到核因子κB受体活化因子配体刺激后，肥胖小鼠的BMM产生的白细胞介素（IL）-10水平低于瘦小鼠的BMM。在肥胖小鼠的BMM中中和IL-10，在增加破骨细胞（OC）形成方面不如在瘦小鼠的BMM中有效。外源性IL-10在肥胖小鼠的BMM中比在瘦小鼠的BMM中更强烈地抑制OC形成。因此，肥胖小鼠的BMM中OC形成水平升高可能部分归因于IL-10水平降低，IL-10是破骨细胞生成的负调节因子。我们的结果表明，肥胖与骨质流失有关，这是由于肥胖小鼠的BMM产生的IL-10减少，导致破骨细胞生成增强。
