Transgenic expression of n-3 fatty acid desaturase (fat-1) in C57/BL6 mice: Effects on glucose homeostasis and body weight.
The fat-1 gene, derived from Caenorhabditis elegans, encodes for a fatty acid n-3 desaturase. In order to study the potential metabolic benefits of n-3 fatty acids, independent of dietary fatty acids, we developed seven lines of fat-1 transgenic mice (C57/BL6) controlled by the regulatory sequences of the adipocyte protein-2 (aP2) gene for adipocyte-specific expression (AP-lines). We were unable to obtain homozygous fat-1 transgenic offspring from the two highest expressing lines, suggesting that excessive expression of this enzyme may be lethal during gestation. Serum fatty acid analysis of fat-1 transgenic mice (AP-3) fed a high n-6 unsaturated fat (HUSF) diet had an n-6/n-3 fatty acid ratio reduced by 23% (P < 0.025) and the n-3 fatty acid eicosapentaenoic acid (EPA) concentration increased by 61% (P < 0.020). Docosahexaenoic acid (DHA) was increased by 19% (P < 0.015) in white adipose tissue. Male AP-3-fat-1 line of mice had improved glucose tolerance and reduced body weight with no change in insulin sensitivity when challenged with a high-carbohydrate (HC) diet. In contrast, the female AP-3 mice had reduced glucose tolerance and no change in insulin sensitivity or body weight. These findings indicate that male transgenic fat-1 mice have improved glucose tolerance likely due to increased insulin secretion while female fat-1 mice have reduced glucose tolerance compared to wild-type mice. Finally the inability of fat-1 transgenic mice to generate homozygous offspring suggests that prolonged exposure to increased concentrations of n-3 fatty acids may be detrimental to reproduction.
Ji
Shaonin
S
Department of Genetics, University of Alabama at Birmingham, 35294, USA.
Hardy
Robert W
RW
Wood
Philip A
PA
D000818:Animals; D001835:Body Weight; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000494:pharmacology*; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance; D006706:Homeostasis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012098:Reproduction; D012737:Sex Factors
D029742:Caenorhabditis elegans Proteins; D015525:Fatty Acids, Omega-3; C466741:fat-1 protein, C elegans; D044943:Fatty Acid Desaturases; D005947:Glucose