10,12-Tricosadiynoic acid is a highly specific, selective, and orally active inhibitor of acyl-CoA oxidase-1 (ACOX1)[1]. ACOX1 functions in peroxisomes, primarily responsible for fatty acid metabolism, especially the β-oxidation of long-chain fatty acids, and plays a crucial role in maintaining cellular health and lipid homeostasis[2]. 10,12-Tricosadiynoic acid can be used to treat metabolic diseases (such as those induced by obesity) by improving lipid and reactive oxygen species (ROS) metabolism, and serves as a click chemistry reagent due to its alkyne group[3,4].
In vitro, treatment of HL-7702 and HEP-G2 cells with 10,12-Tricosadiynoic acid (500nM) together with GW4064 for 48h effectively reversed the GW4064-induced upregulation of ACOX1 protein and mRNA expression[5]. Treatment of SiHa and HCT116 cancer cells cultured in an acidic environment (pH 6.5) with 10,12-Tricosadiynoic acid (60μM) combined with docosahexaenoic acid (DHA, 50μM) for 24h significantly reduced cell viability[6].
In vivo, oral administration of 10,12-Tricosadiynoic acid (100μg/kg/day) to Wistar rats fed a high-fat diet (HFD) for 8 weeks significantly reduced body weight gain, decreased liver weight and triglyceride content, and alleviated hepatic steatosis[1]. Oral administration of 10,12-Tricosadiynoic acid (100mg/kg/day) for 4 weeks to diabetic mice chronically fed high erucic acid rapeseed oil (HRO) significantly inhibited hepatic peroxisomal β-oxidation and cholesterol synthesis, and reduced plasma very low-density lipoprotein cholesterol levels[7].
References:
[1] ZENG J, DENG S, WANG Y, 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]. Journal of Biological Chemistry, 2017, 292(9): 3800-3809.
[2] LU D, HE A, TAN M, et al. Liver ACOX1 regulates levels of circulating lipids that promote metabolic health through adipose remodeling[J]. Nature Communications, 2024, 15(1): 4214.
[3] LIU Y, HAN S L, LUO Y, et al. Impaired peroxisomal fat oxidation induces hepatic lipid accumulation and oxidative damage in Nile tilapia[J]. Fish Physiology and Biochemistry, 2020, 46(4): 1229-1242.
[4] CHEN X, ZHOU G, PENG X, et al. Biosensors and chemosensors based on the optical responses of polydiacetylenes[J]. Chemical Society Reviews, 2012, 41(13): 4610-4630.
[5] YANG Y, YUAN W, HE K, et al. Inhibition of ACOX1 enhances the therapeutic efficacy of obeticholic acid in treating non-alcoholic fatty liver disease and mitigates its lipotoxicity[J]. Frontiers in Pharmacology, 2024, 15: 1366479.
[6] IBANEZ S, GIOLITO M V, AL-SIYABI S, et al. Acidosis forces fatty acid uptake and metabolism in cancer cells regardless of genotype[J]. Advanced Science, 2025, 12(40): e05436.
[7] ZHANG X, WANG Y, YAO H, et al. Peroxisomal β-oxidation stimulates cholesterol biosynthesis in the liver in diabetic mice[J]. Journal of Biological Chemistry, 2022, 298(2): 101572.
10,12-Tricosadiynoic acid是一种具有高效特异性、选择性和口服活性的酰基辅酶A氧化酶-1（ACOX1）抑制剂[1]。ACOX1在过氧化物酶体中发挥作用，主要负责脂肪酸代谢，特别是长链脂肪酸的β-氧化，对维持细胞健康和脂质稳态至关重要[2]。10,12-Tricosadiynoic acid可用于通过改善脂质和活性氧（ROS）代谢治疗代谢疾病（如肥胖引起的问题），并因其烯烃基团起到点击化学试剂作用[3,4]。
在体外，10,12-Tricosadiynoic acid（500nM）与GW4064共同处理HL-7702和HEP-G2细胞48h，有效逆转了由GW4064诱导的ACOX1蛋白和mRNA表达上调[5]。10,12-Tricosadiynoic acid（60μM）与二十二碳六烯酸（DHA, 50μM）联合处理处于酸性环境（pH 6.5）的SiHa和HCT116癌细胞24h，显著降低了细胞活力[6]。
在体内，10,12-Tricosadiynoic acid（100μg/kg/day）通过口服治疗高脂饮食（HFD）喂养的Wistar大鼠8周，能显著降低体重增加、减少肝脏重量和甘油三酯含量，并减轻肝脏脂肪变性[1]。10,12-Tricosadiynoic acid（100mg/kg/day）连续口服给药4周给长期喂养高芥酸菜籽油（HRO）的糖尿病小鼠，显著抑制了肝脏过氧化物酶体β-氧化和胆固醇合成，并降低了血浆极低密度脂蛋白胆固醇水平[7]。