Elovl6, also known as elongation of very-long-chain fatty acids protein 6, is a microsomal enzyme. It is involved in the elongation of saturated and monounsaturated fatty acids, converting C12-C16 fatty acids to C18 fatty acids [2,4,6]. This process is crucial for regulating fatty acid composition in cells, which impacts various biological processes, including energy metabolism, immune responses, and lipid biosynthesis pathways [1-7]. Gene-knockout (KO) mouse models have been valuable in studying its function.

In KO mouse models, Elovl6 deficiency has shown diverse effects. In allergic airway inflammation, Elovl6-deficient mice had enhanced inflammation, with increased lymphocyte egress from lymph nodes and upregulated type 2 and non-type 2 immune responses. Lipidomic profiling revealed higher levels of palmitic acid, ceramides, and sphingosine-1-phosphate in their lungs, indicating its role in regulating the ceramide-S1P pathway [1]. In diabetes-related studies, Elovl6-deficient mice mated to leptin receptor-deficient db/db mice were protected against obesity-induced insulin resistance or β-cell failure, despite similar hepatosteatosis and obesity, suggesting Elovl6 as a metabolic checkpoint [2,4,6]. In pancreatic cancer, genetic or chemical inhibition of ELOVL6 reduced tumor cell proliferation and migration, increased Abraxane uptake, and suppressed tumor growth in vivo, positioning it as a potential therapeutic target [3]. In multiple sclerosis, depletion of Elovl6 in phagocytes induced a repair-promoting phenotype, prevented demyelination, and boosted remyelination [5].

In conclusion, Elovl6 is a key enzyme in fatty acid metabolism. Through model-based research, especially KO mouse models, its importance in various disease areas has been revealed, including allergic airway inflammation, diabetes, pancreatic cancer, and multiple sclerosis. These findings suggest that targeting Elovl6 could be a potential therapeutic approach for these diseases.

References:

1. Yoshida, Kazufumi, Morishima, Yuko, Ano, Satoshi, Shimano, Hitoshi, Hizawa, Nobuyuki. 2022. ELOVL6 deficiency aggravates allergic airway inflammation through the ceramide-S1P pathway in mice. In The Journal of allergy and clinical immunology, 151, 1067-1080.e9. doi:10.1016/j.jaci.2022.12.808. https://pubmed.ncbi.nlm.nih.gov/36592705/

2. Matsuzaka, Takashi. 2020. Role of fatty acid elongase Elovl6 in the regulation of energy metabolism and pathophysiological significance in diabetes. In Diabetology international, 12, 68-73. doi:10.1007/s13340-020-00481-3. https://pubmed.ncbi.nlm.nih.gov/33479581/

3. García García, Ana, Ferrer Aporta, María, Vallejo Palma, Germán, Rodríguez Peralto, José Luis, Sánchez-Arévalo Lobo, Víctor Javier. 2025. Targeting ELOVL6 to disrupt c-MYC driven lipid metabolism in pancreatic cancer enhances chemosensitivity. In Nature communications, 16, 1694. doi:10.1038/s41467-025-56894-8. https://pubmed.ncbi.nlm.nih.gov/39956817/

4. Matsuzaka, Takashi, Shimano, Hitoshi. 2009. Elovl6: a new player in fatty acid metabolism and insulin sensitivity. In Journal of molecular medicine (Berlin, Germany), 87, 379-84. doi:10.1007/s00109-009-0449-0. https://pubmed.ncbi.nlm.nih.gov/19259639/

5. Garcia Corrales, Aida V, Verberk, Sanne G S, Haidar, Mansour, Bogie, Jeroen F J, Hendriks, Jerome J A. 2023. Fatty acid elongation by ELOVL6 hampers remyelination by promoting inflammatory foam cell formation during demyelination. In Proceedings of the National Academy of Sciences of the United States of America, 120, e2301030120. doi:10.1073/pnas.2301030120. https://pubmed.ncbi.nlm.nih.gov/37669365/

6. Matsuzaka, Takashi, Shimano, Hitoshi. . [Role of Fatty Acid Elongase Elovl6 in the Regulation of Fatty Acid Quality and Lifestyle-related Diseases]. In Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 142, 473-476. doi:10.1248/yakushi.21-00176-4. https://pubmed.ncbi.nlm.nih.gov/35491151/