Etomoxir is an irreversible inhibitor of carnitine palmitoyltransferase 1a (CPT-1a). Etomoxir inhibits fatty acid oxidation (FAO) and palmitate oxidation via CPT-1a[1].
T cells cultured in low-glucose medium in the presence of Etomoxir (100μM) significantly reduce interferon gamma (IFN-γ) production and do not promote T-helper 2 (Th2)-related cytokine IL-4 production, while Etomoxir has no effect on T cells cultured in high-glucose medium[2]. Etomoxir (500μM) can significantly inhibit FAO in A549 and A549T cells. Etomoxir at 500μM or 1mM can significantly increase the sensitivity of paclitaxel-resistant cells (A549T) to paclitaxel[3].
In experimental autoimmune encephalomyelitis (EAE) mice, Etomoxir (15mg/kg) reduces inflammatory responses, immune cell infiltration in the central nervous system (CNS), as well as inflammation and demyelination in the CNS[2]. In C57BLKS/J lar-Leprdb/db and high-fat (HF)-fed mice, Etomoxir (1mg/kg) significantly reduces the decrease in bone mineral density (BMD) and bone-breaking strength, and inhibits the decrease in osteoblasts differentiated from bone marrow stromal cells (BMSCs)[4].
References:
[1] Rupp H, et al. The use of partial fatty acid oxidation inhibitors for metabolic therapy of angina pectoris and heart failure. Herz. 2002 Nov;27(7):621-36.
[2] Shriver L P, Manchester M. Inhibition of fatty acid metabolism ameliorates disease activity in an animal model of multiple sclerosis[J]. Scientific reports, 2011, 1(1): 79.
[3] Li J, Zhao S, Zhou X, et al. Inhibition of lipolysis by mercaptoacetate and etomoxir specifically sensitize drug-resistant lung adenocarcinoma cell to paclitaxel[J]. PloS one, 2013, 8(9): e74623.
[4] Li J, He W, Liao B, et al. FFA-ROS-P53-mediated mitochondrial apoptosis contributes to reduction of osteoblastogenesis and bone mass in type 2 diabetes mellitus[J]. Scientific reports, 2015, 5(1): 12724.
Etomoxir是肉碱棕榈酰转移酶1a（CPT-1a）的不可逆抑制剂。Etomoxir可通过CPT-1a抑制脂肪酸氧化（FAO）和棕榈酸酯氧化[1]。
在低糖培养基中培养的T细胞在Etomoxir（100μM）存在下，可显著减少干扰素γ（IFN-γ）的产生，并且不会促进T-helper 2（Th2）相关细胞因子IL-4的产生，而Etomoxir对高糖培养基中培养的T细胞没有影响[2]。Etomoxir（500μM）可明显抑制A549和A549T细胞中的FAO。500μM或1mM的Etomoxir可明显提高紫杉醇耐药细胞（A549T）对紫杉醇的敏感性[3]。
在实验性自身免疫性脑脊髓炎（EAE）小鼠中，Etomoxir（15mg/kg）可减少小鼠炎症反应、中枢神经系统中的免疫细胞浸润以及中枢神经系统的炎症和脱髓鞘[2]。在C57BLKS/J lar-Leprdb/db和高脂肪（HF）喂养的小鼠中，Etomoxir（1mg/kg）可显著减少骨矿物质密度（BMD）和破骨强度的下降，抑制骨髓基质干细胞（BMSCs）分化的成骨细胞的减少[4]。