Grant: Travel Awards - Institute Community Support

Not all dietary fats may be safe for chronic use. Studies in both humans and animals have shown that n-6 polyunsaturated fatty acids (n-6 PUFA), found in high amounts in oils such as corn and safflower oil, may harm the heart. However, how such toxicity is induced remains unknown. One difficulty to understanding the specific effects of these fatty acids is that high fat diets make animals fat which in turn can cause independent effects within the mammalian heart muscle. As the fruit fly, Drosophila melanogaster does not require dietary lipids for its nutrition; the effects of n-6 PUFA in its nerve bundles (similar to the heart in mammals) may represent an unique way to identify nutrition-independent effects of n-6 PUFA. As corn oil has high n-6 PUFA and olive oil has very low amounts of these fatty acids, we compared the responses to oxidative stress after a 5-day diet (5% w/w of either corn or olive oil) in Drosophila and a 5-week high-fat diet (40% w/w of olive or corn oil) in mice. After feeding, to induce stress, flies were exposed to 100% oxygen for 12 hours. In mice, a dose of isoproteronol (100mg/kg) was administered, that induced a whole-body stress responses for over 12 hours. Following such stresses, flies fed corn oil had decreased survival compared to olive oil fed flies. In mice, isoproteronol treatment also lowered heart function in corn oil fed mice only. In both flies and mice, genes responsible for damage repair were reduced only in corn oil fed flies or mice. Overall, these results demonstrate that the mechanisms involved in the toxic response to n-6 PUFA may be similar in both flies and mice following stress. Therefore flies, with their rapid generation time and low costs for maintenance could be a useful alternate model to study the effects of dietary fats, independent of nutritional effects, as demonstrated in our fly model.