Abstract
Transgenic mice (named “Omega mice”) were engineered to carry both optimized fat-1 and fat-2 genes from the roundworm Caenorhabditis elegans and are capable of producing essential omega-6 and omega-3 fatty acids from saturated fats or carbohydrates. When maintained on a high-saturated fat diet lacking essential fatty acids or a high-carbohydrate, no-fat diet, the Omega mice exhibit high tissue levels of both omega-6 and omega-3 fatty acids, with a ratio of ∼1∶1. This study thus presents an innovative technology for the production of both omega-6 and omega-3 essential fatty acids, as well as a new animal model for understanding the true impact of fat on human health.
Highlights
There are several classes of fats that differentially affect human health, such as saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA), including both essential omega-6 (n-6) and omega-3 (n-3) PUFA
Recent studies have indicated that the tissue n-6/n-3 PUFA ratio plays an important role in the pathogenesis of many chronic diseases [2],[7]
To enable the higher expression of the C. elegans fat-2 gene in mammals, we first optimized the codon of the fat-2 sequence based on the mammalian desaturase sequence (Figure S1) and utilized a chicken beta-actin promoter to build a transgene construct (Figure S2), and used microinjection to create the fat-2 transgenic mouse
Summary
There are several classes of fats that differentially affect human health, such as saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA), including both essential omega-6 (n-6) and omega-3 (n-3) PUFA. The primary essential fatty acids in the diet are n-6 linoleic acid (18:2n6, LA) and n-3 a-linolenic acid (18:3n-3, ALA), which can be converted into longer-chain n-6 PUFA arachidonic acid (20:4n-6, AA) and n-3 PUFA eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA), respectively, through a series of desaturation and chain-elongation enzyme systems [5]. Since the synthesis of n-6 and n-3 long-chain PUFA and their metabolites compete for the same enzymes, their ratio in body tissues determines the eicosanoid profile. Recent studies have indicated that the tissue n-6/n-3 PUFA ratio plays an important role in the pathogenesis of many chronic diseases [2],[7]. It is often challenging to balance the different types of dietary fat in a way that optimizes health
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