Acaca, also known as acetyl-CoA carboxylase 1, is a key rate-limiting enzyme in fatty acid synthesis. It catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, which is crucial for de novo lipogenesis. This process is associated with various metabolic pathways and is of great biological importance in lipid metabolism [5]. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, are valuable for studying its functions.

In a fatty liver mouse model, inhibiting Acaca reduced intracellular lipid accumulation, improved mitochondrial function, and alleviated oxidative stress via the AMPK-PPARα-CPT1A axis [1]. In prostate cancer, ND630 controlled Acaca and lipid reprogramming by regulating the expression of circKIF18B_003, which increased Acaca expression by sponging miR-370-3p [2]. Down-regulation of Acaca in prostate cancer cells suppressed their malignant progression, reducing proliferation and mitochondrial potential [3]. In cervical cancer, circ-Acaca promoted cell proliferation, invasion, migration, and glycolysis by targeting the miR-582-5p/ERO1A signaling axis [4].

In conclusion, Acaca is essential for fatty acid synthesis and lipid metabolism. Model-based research, especially KO/CKO mouse models, has revealed its significant roles in diseases like non-alcoholic fatty liver disease and various cancers. Understanding Acaca's functions provides potential therapeutic targets for these diseases.

References:

1. Dong, Jian, Li, Muzi, Peng, Runsheng, Qiao, Zilin, Sun, Na. 2024. ACACA reduces lipid accumulation through dual regulation of lipid metabolism and mitochondrial function via AMPK- PPARα- CPT1A axis. In Journal of translational medicine, 22, 196. doi:10.1186/s12967-024-04942-0. https://pubmed.ncbi.nlm.nih.gov/38395901/

2. Wu, Yu-Peng, Zheng, Wen-Cai, Huang, Qi, Xue, Xue-Yi, Xu, Ning. 2023. ND630 controls ACACA and lipid reprogramming in prostate cancer by regulating the expression of circKIF18B_003. In Journal of translational medicine, 21, 877. doi:10.1186/s12967-023-04760-w. https://pubmed.ncbi.nlm.nih.gov/38049827/

3. Zhang, Hui, Liu, Shaoyou, Cai, Zhouda, Tan, Huijing, Zhong, Weide. 2021. Down-regulation of ACACA suppresses the malignant progression of Prostate Cancer through inhibiting mitochondrial potential. In Journal of Cancer, 12, 232-243. doi:10.7150/jca.49560. https://pubmed.ncbi.nlm.nih.gov/33391420/

4. Huang, Dandan, Li, Cuimei. 2021. circ-ACACA promotes proliferation, invasion, migration and glycolysis of cervical cancer cells by targeting the miR-582-5p/ERO1A signaling axis. In Oncology letters, 22, 795. doi:10.3892/ol.2021.13056. https://pubmed.ncbi.nlm.nih.gov/34584570/

5. Chen, Leyuan, Duan, Yuqing, Wei, Huiqiang, Qin, Yong, Li, Yiliang. 2019. Acetyl-CoA carboxylase (ACC) as a therapeutic target for metabolic syndrome and recent developments in ACC1/2 inhibitors. In Expert opinion on investigational drugs, 28, 917-930. doi:10.1080/13543784.2019.1657825. https://pubmed.ncbi.nlm.nih.gov/31430206/