Fads1-flox Mouse

Fads1, also known as Delta-5 desaturase, is a rate-limiting enzyme in long-chain polyunsaturated fatty acid (LCPUFA) synthesis [1,3]. It is involved in the biosynthesis of arachidonic acid (AA), an essential polyunsaturated fatty acid. Fads1-associated pathways include the conversion of AA to prostaglandin E2 (PGE2) via the TLR4/MYD88 pathway in colorectal cancer cells, and it also plays a role in lipid metabolism, which is related to various biological processes and diseases [1].

In colorectal cancer, AA feeding promotes tumor growth in AOM/DSS and intestinal-specific Apc-/-mice. Fads1 is upregulated in CRC, and it effectively mediates AA synthesis. Functionally, Fads1 regulates CRC tumor growth through a high AA microenvironment-induced enrichment of gram-negative microbes. Eliminating gram-negative microbes abolishes the Fads1 effect [1].

In triple-negative breast cancer, Fads1/2 are highly expressed in a subset of TNBC with a poorer prognosis. Targeting Fads1/2 by genetic interference and pharmacological approaches renders tumors ferroptosis-resistant [2].

In hepatocyte-specific models, AAV8-mediated overexpression of Fads1 in rats fed a high-fat high-fructose diet reduced plasma triglyceride and hepatic cholesterol levels, while in low-fat high-fructose diet-fed rats, it improved glucose tolerance and insulin signaling [3].

In conclusion, Fads1 is crucial for LCPUFA synthesis and lipid metabolism. Its dysregulation is associated with various diseases such as colorectal cancer, triple-negative breast cancer, and metabolic syndrome-related conditions. Mouse models, including those with altered Fads1 expression, have revealed its role in tumor growth regulation, ferroptosis susceptibility, and metabolic phenotype modulation, providing insights into disease mechanisms and potential therapeutic targets.