Atglistatin is a selective adipose triglyceride lipase (ATGL) inhibitor (IC50 = 0.7μM) [1]. Atglistatin inhibits ATGL and reduces the decomposition of triglycerides, thereby affecting the release of fatty acids and energy metabolism [2]. Atglistatin is mainly used to treat myocardial damage [3].
In B16-F10, C26, CT26, LLC, and HepG2 cells, Atglistatin (40μM; 50h, 100h, 150h) treatment reduced proliferation of all cancer cells [4]. In HT29 cells, Atglistatin (40μM; 24h) inhibits the migration and growth of colon cancer cells [5]. In A549 cells, Atglistatin (50μM, 100μM; 24h) slows the growth of cancer cells [6].
In isoprenaline mouse model, Atglistatin (2mM/kg; po; 7d, 14d) exerts its cardioprotective effects by modulating fatty acid release from white adipose tissue [3]. In isoprenaline (ISO) mouse model, Atglistatin (2mM/kg; po; 7d) ameliorates ISO-induced cardiac hypertrophy and fibrosis [7]. In the myocardial infarction model, Atglistatin (100µM/kg; po; 2d) treated mice showed significant improvement in cardiac systolic pump function [8].
References:
[1]. Mayer N, Schweiger M, Romauch M, et al. Development of small-molecule inhibitors targeting adipose triglyceride lipase. Nature chemical biology. 2013 Dec; 9(12): 785-787.
[2]. Han SL, Liu Y, Limbu SM, et al. The reduction of lipid-sourced energy production caused by ATGL inhibition cannot be compensated by activation of HSL, autophagy, and utilization of other nutrients in fish. Fish Physiology and Biochemistry. 2021 Feb; 47: 173-188.
[3]. Thiele A, Luettges K, Ritter D, et al. Pharmacological inhibition of adipose tissue adipose triglyceride lipase by Atglistatin prevents catecholamine-induced myocardial damage. Cardiovascular research. 2022 Jul 1; 118(11): 2488-2505.
[4]. Xie H, Heier C, Kien B, et al. Adipose triglyceride lipase activity regulates cancer cell proliferation via AMP-kinase and mTOR signaling. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids. 2020 Sep 1; 1865(9): 158737.
[5]. Iftikhar R, Penrose HM, King AN, et al. Elevated ATGL in colon cancer cells and cancer stem cells promotes metabolic and tumorigenic reprogramming reinforced by obesity. Oncogenesis. 2021 Nov 29; 10(11): 82.
[6]. Zagani R, El-Assaad W, Gamache I, et al. Inhibition of adipose triglyceride lipase (ATGL) by the putative tumor suppressor G0S2 or a small molecule inhibitor attenuates the growth of cancer cells. Oncotarget. 2015 Jul 31; 6(29): 28282.
[7]. Takahara S, Ferdaoussi M, Srnic N, et al. Inhibition of ATGL in adipose tissue ameliorates isoproterenol-induced cardiac remodeling by reducing adipose tissue inflammation. American Journal of Physiology-Heart and Circulatory Physiology. 2021 Jan 1; 320(1): H432-H446.
[8]. Bottermann K, Granade ME, Oenarto V, et al. Atglistatin pretreatment preserves remote myocardium function following myocardial infarction. Journal of Cardiovascular Pharmacology and Therapeutics. 2021 May; 26(3): 289-297.
Atglistatin是一种选择性脂肪甘油三酯脂肪酶（ATGL）抑制剂（IC50 = 0.7μM） [1]。Atglistatin 抑制ATGL并减少甘油三酯的分解，从而影响脂肪酸的释放和能量代谢 [2]。Atglistatin主要用于治疗心肌损伤 [3]。
在B16-F10、C26、CT26、LLC和HepG2细胞中，Atglistatin（40μM；50h、100h、150h）处理可降低所有癌细胞的增殖 [4]。在HT29细胞中，Atglistatin（40μM；24h）可抑制结肠癌细胞的迁移和生长 [5]。在A549细胞中，Atglistatin（50μM、100μM；24h）可减缓癌细胞的生长 [6]。
在异丙肾上腺素小鼠模型中，Atglistatin（2mM/kg；po；7d、14d）通过调节白色脂肪组织脂肪酸的释放发挥其心脏保护作用 [3]。在异丙肾上腺素（ISO）小鼠模型中，Atglistatin（2mM/kg；po；7d）可改善ISO诱导的心脏肥大和纤维化 [7]。在心肌梗死模型中，Atglistatin（100µM/kg；po；2d）治疗的小鼠心脏收缩泵功能显著改善 [8]。