Acaa1a-KO Mouse

Acaa1a, also known as acetyl-CoA acyltransferase 1A, is a crucial rate-limiting enzyme in the process of fatty acid β-oxidation [1]. It is involved in lipid metabolism pathways, which are essential for maintaining normal physiological functions related to energy production from fatty acids. Genetic models, such as KO or CKO mouse models, can be valuable in studying its function in vivo.

In the context of various disease-related studies, its expression has been shown to be affected in multiple conditions. In mouse livers infected with Babesia microti, the expression of Acaa1a was downregulated, along with other key enzymes in fatty acid β-oxidation, suggesting its role in the molecular mechanisms underlying liver injury and self-repair during infection [1]. In D-Gal induced mice, the relative mRNA levels of Acaa1a were significantly up-regulated in groups treated with peony seed oil or fish oil, which are rich in n-3 PUFA, and this was associated with the inhibition of neuroinflammation through the PPAR/RXR signaling pathway [2]. Dietary phospholipids, especially EPA-PLs and PSs, were found to reduce fat accumulation in high-fat-diet-fed mice by enhancing the expression of Acaa1a, among other genes involved in fatty acid β-oxidation [3]. In a rat model of gestational diabetes mellitus, the placental expression of Acaa1a was significantly upregulated, along with other genes related to fatty acid β-oxidation, suggesting its role in the altered placental fatty acid metabolism and transport [4]. In CCl4-treated mice, the decreased expression of Acaa1a was related to the dysregulation of purine degradation in acute hepatitis [5]. In rats with alcohol-induced fatty liver, dietary umbelliferone attenuated the condition by up-regulating the expression of Acaa1a, among other fatty acid oxidation genes, and down-regulating lipogenic genes [6]. In another study on alcohol-induced lipid dysmetabolism and inflammation in rats, scopoletin increased the expression of Acaa1a, among other fatty acid oxidative genes, in both white adipose tissue and liver [7].

In conclusion, Acaa1a is essential for fatty acid β-oxidation and lipid metabolism. Studies using mouse models have revealed its significance in various disease conditions such as infections, neuroinflammation, obesity, gestational diabetes, and liver-related diseases. Understanding Acaa1a function through these models provides insights into the molecular mechanisms underlying these diseases and may offer potential targets for therapeutic intervention.

References:

1. Hu, Yuhong, Wang, Minjing, Ren, Shuguang, Wang, Hui, Liu, Jingze. 2020. Quantitative proteomics and phosphoproteomic analyses of mouse livers after tick-borne Babesia microti infection. In International journal for parasitology, 51, 167-182. doi:10.1016/j.ijpara.2020.09.002. https://pubmed.ncbi.nlm.nih.gov/33242464/

2. Zhang, Tianyu, Zhang, Ying, Ji, Andong, Li, Huiying, Zeng, Qiangcheng. 2025. Peony Seed Oil Inhibited Neuroinflammation by PPAR/RXR Signaling Pathway in D-Gal Induced Mice. In Food science & nutrition, 13, e70000. doi:10.1002/fsn3.70000. https://pubmed.ncbi.nlm.nih.gov/40018014/

3. Zhang, Lingyu, Mu, Jiaqin, Meng, Jing, Su, Wenjin, Li, Jian. 2023. Dietary Phospholipids Alleviate Diet-Induced Obesity in Mice: Which Fatty Acids and Which Polar Head. In Marine drugs, 21, . doi:10.3390/md21110555. https://pubmed.ncbi.nlm.nih.gov/37999379/

4. Mishra, Jay S, Kumar, Sathish. 2023. Placental Fatty Acid Metabolism and Transport in a Rat Model of Gestational Diabetes Mellitus. In Journal of women's health and development, 6, 56-67. doi:10.26502/fjwhd.2644-288400108. https://pubmed.ncbi.nlm.nih.gov/37288271/

5. Wang, Tianyu, Hu, Longlong, Lu, Jiongjiong, Xia, Huiyu, Lu, Haitao. 2022. Functional metabolomics revealed functional metabolic-characteristics of chronic hepatitis that is significantly differentiated from acute hepatitis in mice. In Pharmacological research, 180, 106248. doi:10.1016/j.phrs.2022.106248. https://pubmed.ncbi.nlm.nih.gov/35537579/

6. Kim, Myung-Joo, Sim, Mi-Ok, Lee, Hae-In, Seo, Kwon-Il, Lee, Mi-Kyung. 2014. Dietary umbelliferone attenuates alcohol-induced fatty liver via regulation of PPARα and SREBP-1c in rats. In Alcohol (Fayetteville, N.Y.), 48, 707-15. doi:10.1016/j.alcohol.2014.08.008. https://pubmed.ncbi.nlm.nih.gov/25262573/

7. Lee, Hae-In, Lee, Mi-Kyung. 2015. Coordinated regulation of scopoletin at adipose tissue-liver axis improved alcohol-induced lipid dysmetabolism and inflammation in rats. In Toxicology letters, 237, 210-8. doi:10.1016/j.toxlet.2015.06.016. https://pubmed.ncbi.nlm.nih.gov/26115886/