Elovl1-KO Mouse

Elovl1, or elongation of very long-chain fatty acids protein 1, is an enzyme that catalyzes the rate-limiting step in the synthesis of very long-chain fatty acids (VLCFAs). It is involved in the elongation of saturated and monounsaturated fatty acids, influencing lipid metabolism. Its activity is also linked to the synthesis of C24 sphingolipids [3,5].

In a mouse model of acute axonal injury, astrocyte-specific knockout of Elovl1, the saturated lipid synthesis enzyme, mitigated astrocyte-mediated toxicity, suggesting that it plays a role in the mechanism by which neurotoxic reactive astrocytes induce cell death via saturated lipids [1]. In hepatocellular carcinoma, silencing Elovl1 in cell lines inhibited cell growth, promoted apoptosis, and decreased metastasis and invasion. In a xenograft model, low expression of Elovl1 inhibited tumor growth, indicating its role in promoting tumor growth through regulating the PI3K-AKT-mTOR signaling pathway [2]. In CD8+ T cells, inactivation of Elovl1 combined with anti-PD-1 showed therapeutic efficacy in resistant pancreatic and melanoma tumors, enhancing T cell fitness in solid tumours [4].

In conclusion, Elovl1 is crucial for lipid metabolism and the synthesis of specific sphingolipids. Its study using knockout models has revealed its significant roles in neurodegenerative processes, cancer development, and T cell-related immunotherapy. These findings highlight the potential of targeting Elovl1 for therapeutic interventions in relevant disease areas.

References:

1. Guttenplan, Kevin A, Weigel, Maya K, Prakash, Priya, Liddelow, Shane A, Barres, Ben A. 2021. Neurotoxic reactive astrocytes induce cell death via saturated lipids. In Nature, 599, 102-107. doi:10.1038/s41586-021-03960-y. https://pubmed.ncbi.nlm.nih.gov/34616039/

2. Qin, Liang, Song, Cheng-Ze, Yuan, Fa-Yang, Ma, Yi-Fei, Chen, Zi-Li. 2024. ELOVL1 is upregulated and promotes tumor growth in hepatocellular carcinoma through regulating PI3K-AKT-mTOR signaling. In Heliyon, 10, e34961. doi:10.1016/j.heliyon.2024.e34961. https://pubmed.ncbi.nlm.nih.gov/39144963/

3. Siddiqui, Arif Jamal, Kumar, Vikash, Jahan, Sadaf, Snoussi, Mejdi, Adnan, Mohd. 2023. Computational insight into structural basis of human ELOVL1 inhibition. In Computers in biology and medicine, 157, 106786. doi:10.1016/j.compbiomed.2023.106786. https://pubmed.ncbi.nlm.nih.gov/36924735/

4. Pretto, Samantha, Yu, Qian, Bourdely, Pierre, Di Matteo, Mario, Mazzone, Massimiliano. 2025. A functional single-cell metabolic survey identifies Elovl1 as a target to enhance CD8+ T cell fitness in solid tumours. In Nature metabolism, 7, 508-530. doi:10.1038/s42255-025-01233-w. https://pubmed.ncbi.nlm.nih.gov/40065102/

5. Ohno, Yusuke, Suto, Shota, Yamanaka, Masao, Sassa, Takayuki, Kihara, Akio. 2010. ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis. In Proceedings of the National Academy of Sciences of the United States of America, 107, 18439-44. doi:10.1073/pnas.1005572107. https://pubmed.ncbi.nlm.nih.gov/20937905/