Wang Yan, Zhou Fangli, Shu Siyi, Wu Yunhong, Tian Haoming, Li Yujue, Chen Xiang
Laboratory of Endocrinology and Metabolism, Department of Endocrinology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Department of Geriatric Medicine, The People's Hospital of Deyang City, Deyang, 618000, China.
Biochem Biophys Rep. 2024 Jul 13;39:101788. doi: 10.1016/j.bbrep.2024.101788. eCollection 2024 Sep.
Non-alcoholic fatty liver disease (NAFLD) is associated with abnormal bone metabolism, potentially mediated by elevated levels of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-ɑ) and interleukin 6 (IL-6). This study aims to investigate the direct regulatory effects of liver tissues on osteoblast and osteoclast functions , focusing on the liver-bone axis in NAFLD. Twelve-week-old C57BL/6 mice were fed either a control diet or a high-fat diet (HFD) for 12 weeks. Bone structural parameters were assessed using microCT. Primary hepatocyte cultures were established from control and HFD-fed C57BL/6 mice, as well as IL-6 and TNF-α mice. The supernatants from these hepatocyte cultures were used to induce differentiation in bone marrow cell-derived osteoblasts and osteoclasts . Results showed that mice on a HFD exhibited increased lipid infiltration in liver and bone marrow tissues, alongside reduced bone mass. Moreover, the supernatants from hepatocyte cultures from mice on a HFD displayed elevated TNF-α and IL-6 levels. These supernatants, particularly those derived from HFD-fed and IL-6 mice, significantly enhanced osteoclast differentiation . In contrast, supernatants from TNF-α mice did not significantly affect osteoblast or osteoclast differentiation . In conclusions, this current study suggested that fatty liver tissues may negatively impact bone metabolism. Additionally, knockout of and genes revealed distinct influence on osteoblast and osteoclast functions, highlighting the complex interplay between live pathology and bone health.
非酒精性脂肪性肝病（NAFLD）与骨代谢异常有关，可能由肿瘤坏死因子α（TNF-α）和白细胞介素6（IL-6）等促炎细胞因子水平升高介导。本研究旨在探讨肝组织对成骨细胞和破骨细胞功能的直接调节作用，重点关注NAFLD中的肝-骨轴。将12周龄的C57BL/6小鼠分别喂食对照饮食或高脂饮食（HFD）12周。使用显微CT评估骨结构参数。从对照和HFD喂养的C57BL/6小鼠以及IL-6和TNF-α小鼠建立原代肝细胞培养物。这些肝细胞培养物的上清液用于诱导骨髓细胞来源的成骨细胞和破骨细胞分化。结果显示，HFD喂养的小鼠肝脏和骨髓组织中的脂质浸润增加，同时骨量减少。此外，HFD喂养小鼠的肝细胞培养物上清液中TNF-α和IL-6水平升高。这些上清液，特别是来自HFD喂养和IL-6小鼠的上清液，显著增强了破骨细胞分化。相比之下，TNF-α小鼠的上清液对成骨细胞或破骨细胞分化没有显著影响。总之，本研究表明脂肪肝组织可能对骨代谢产生负面影响。此外，敲除 和 基因揭示了对成骨细胞和破骨细胞功能的不同影响，突出了肝脏病理与骨骼健康之间复杂的相互作用。
