Acsl5-KO Mouse

Acsl5, or acyl-CoA synthetase long-chain family member 5, is nuclear-coded and expressed in mitochondria. It catalyzes the formation of fatty acyl-CoAs from long-chain fatty acids (C16-C20) in the endoplasmic reticulum and mitochondrial outer membrane, playing a pleiotropic role in lipid metabolism, which is essential for fatty acid oxidation and lipid synthesis [2]. It is also involved in pathways related to cell apoptosis sensing physiologically [4]. Genetic models like KO/CKO mouse models are valuable for studying its functions.

In non-alcoholic fatty liver disease (NAFLD), hepatic overexpression of Acsl5 suppresses high-fat diet-induced NAFLD, while its depletion exacerbates the condition. This shows that Acsl5-mediated fatty acid oxidation regulated by cytoplasmic SIRT6-mediated deacetylation is crucial for NAFLD progression [1]. In the context of diet-induced obesity, intestinal Acsl5 deficiency in mice leads to increased post-prandial GLP-1 and PYY secretion, reduced food intake, and protection against diet-induced obesity, indicating its role in energy balance regulation [5]. In acute myeloid leukemia (AML), knockdown of Acsl5 in AML cells inhibits cell growth both in vitro and in vivo, suggesting it as a potential prognosis marker and pharmacological target [3].

In summary, Acsl5 is essential for lipid metabolism. Through model-based research, its role in diseases such as NAFLD, diet-induced obesity, and AML has been revealed. These findings from Acsl5 KO/CKO mouse models contribute to understanding the underlying mechanisms in these disease areas, potentially providing new directions for treatment.

References:

1. Hou, Tianyun, Tian, Yuan, Cao, Ziyang, Yang, Yang, Zhu, Wei-Guo. 2022. Cytoplasmic SIRT6-mediated ACSL5 deacetylation impedes nonalcoholic fatty liver disease by facilitating hepatic fatty acid oxidation. In Molecular cell, 82, 4099-4115.e9. doi:10.1016/j.molcel.2022.09.018. https://pubmed.ncbi.nlm.nih.gov/36208627/

2. Luo, Qin, Das, Avash, Oldoni, Federico, Luo, Fei, Fang, Zhenfei. 2023. Role of ACSL5 in fatty acid metabolism. In Heliyon, 9, e13316. doi:10.1016/j.heliyon.2023.e13316. https://pubmed.ncbi.nlm.nih.gov/36816310/

3. Ye, Wenle, Wang, Jinghan, Huang, Jiansong, Sun, Jie, Jin, Jie. 2023. ACSL5, a prognostic factor in acute myeloid leukemia, modulates the activity of Wnt/β-catenin signaling by palmitoylation modification. In Frontiers of medicine, 17, 685-698. doi:10.1007/s11684-022-0942-1. https://pubmed.ncbi.nlm.nih.gov/37131085/

4. Quan, Jing, Bode, Ann M, Luo, Xiangjian. 2021. ACSL family: The regulatory mechanisms and therapeutic implications in cancer. In European journal of pharmacology, 909, 174397. doi:10.1016/j.ejphar.2021.174397. https://pubmed.ncbi.nlm.nih.gov/34332918/

5. Griffin, John D, Zhu, Ying, Reeves, Andrew, Buhman, Kimberly K, Greenberg, Andrew S. 2024. Intestinal Acyl-CoA synthetase 5 (ACSL5) deficiency potentiates postprandial GLP-1 & PYY secretion, reduces food intake, and protects against diet-induced obesity. In Molecular metabolism, 83, 101918. doi:10.1016/j.molmet.2024.101918. https://pubmed.ncbi.nlm.nih.gov/38499083/