10,12-Tricosadiynoic acid 是一种高特异性，选择性，高亲和力且具有口服活性的酰基辅酶 A 氧化酶-1 (ACOX1) 抑制剂。10,12-Tricosadiynoic acid 可通过改善线粒体脂质和 ROS 代谢来治疗高脂饮食或肥胖引起的代谢性疾病。
10,12-Tricosadiynoic acid is a highly specific, selective, high affinity and orally active acyl-CoA oxidase-1 (ACOX1) inhibitor. 10,12-Tricosadiynoic acid can treat high fat diet- or obesity-induced metabolic diseases by improving mitochondrial lipid and ROS metabolism[1].
10,12-Tricosadiynoic acid-CoA rapidly inhibits ACOX1 activity in a time- and concentration-dependent manner. The activity of ACOX1 decreases by nearly 95% after 5 min of incubation with 10 eq of 10,12-Tricosadiynoic acid-CoA. ACOX1 activity is inhibited only if free 10,12-Tricosadiynoic Acid is activated as the CoA thioester, the substrate form. Inhibition of ACOX1 by 10,12-Tricosadiynoic acid-CoA is irreversible. And the kinetics parameters KI and kinact are calculated to be 680 nm and 3.18 min-1, respectively[1]. 10,12-Tricosadiynoic acid is the precursor of 10,12-Tricosadiynoic acid-CoA and is transformed into 10,12-Tricosadiynoic acid-CoA by peroxisomal very long chain acyl-CoA synthetase (VLACS) after entering into cells, and it inhibits ACOX1 in vivo[1].
10,12-Tricosadiynoic acid (100 μg/kg; oral gavage; daily; for 8 weeks; male Wistar rats) treatment increases hepatic mitochondrial fatty acid oxidation (FAO) via activation of the SIRT1-AMPK (adenosine 5′-monophosphate-activated protein kinase) pathway and proliferator activator receptor α and reduces hydrogen peroxide accumulation in high fat diet-fed rats, which significantly decreases hepatic lipid and ROS contents, reduces body weight gain, and decreases serum triglyceride and insulin levels[1]. Animal Model: Male Wistar rats (210-230 g) fed with high fat diet[1]
[1]. Zeng J, et al. Specific Inhibition of Acyl-CoA Oxidase-1 by an Acetylenic Acid Improves Hepatic Lipid and Reactive Oxygen Species (ROS) Metabolism in Rats Fed a High Fat Diet. J Biol Chem. 2017 Mar 3;292(9):3800-3809.
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