脂质代谢
新陈代谢
化学
细胞生物学
脂质积聚
生物化学
生物
作者
Xiangxi Kong,Siyue Tao,Zhongyin Ji,Jie Li,Hui Li,Jian Jin,Yuxia Zhao,Junhui Liu,Fengdong Zhao,Jian Chen,Zhenhua Feng,Binhui Chen,Zhi Shan
摘要
Abstract Lipid metabolism plays a crucial role in maintaining bone homeostasis, particularly in osteoclasts (OCs) formation. Here, we found the expression level of FATP2, a transporter for long-chain and very-long-chain fatty acids, was significantly upregulated during OC differentiation and in the bone marrow of mice fed a high-fat diet (HFD). Notably, the use of FATP2 siRNA or a specific inhibitor (Lipofermata) resulted in significant inhibition of OC differentiation while only slightly affecting osteoblasts (OBs). In pathological models of bone loss induced by LPS or OVX, in vivo treatment with Lipofermata was able to rescue the loss of bone mass by inhibiting OC differentiation. RNA sequencing (RNA-seq) revealed that Lipofermata reduced fatty acid β-oxidation and inhibited energy metabolism, while regulating reactive oxygen species (ROS) metabolism to decrease ROS production, ultimately inhibiting OC differentiation. Treatment with Lipofermata, either in vivo or in vitro, effectively rescued the overactivation of OCs, indicating that FATP2 regulated OC differentiation by modulating fatty acid uptake and energy metabolism. These findings suggested that targeting FATP2 may represent a promising therapeutic approach for pathological osteoporosis.
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