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 with C12 to C16 to those with C18. This process is crucial for lipid metabolism and is associated with various biological pathways related to energy metabolism, insulin sensitivity, and immune responses [1-3, 7]. Gene-knockout (KO) mouse models have been valuable in studying its functions.

In KO mouse models, Elovl6 deficiency has shown significant impacts. In allergic airway inflammation, Elovl6 -/- mice had enhanced airway inflammation with increased lymphocyte egress, up-regulated type 2 and non-type 2 immune responses, and altered lipidomic profiles including higher levels of palmitic acid, ceramides, and sphingosine-1-phosphate. Treatment with inhibitors of ceramide synthase and sphingosine kinase ameliorated the aggravated inflammation, indicating Elovl6's role in controlling allergic airway inflammation via the ceramide-S1P pathway [1]. In metabolic studies, Elovl6 (-/-) mice were resistant to diet-induced insulin resistance despite similar hepatosteatosis and obesity to wild-type mice, suggesting Elovl6's role in insulin sensitivity and energy metabolism [2,3,5]. In multiple sclerosis, depletion of Elovl6 induced a repair-promoting phagocyte phenotype, enhanced lipid efflux, increased production of neurotrophic factors, and reduced inflammatory mediators, preventing demyelination and boosting remyelination [4].

In conclusion, Elovl6 is essential for regulating fatty acid composition and is involved in multiple biological processes such as energy metabolism, insulin sensitivity, and immune-inflammatory responses. The use of Elovl6 KO mouse models has provided insights into its role in diseases like asthma, diabetes, and multiple sclerosis, highlighting its potential as a therapeutic target for these conditions [1-3, 6, 7].