Abstract
Polyunsaturated fatty acids (PUFAs) form an important constituent of all the cell membranes in the body. PUFAs such as arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) form precursors to both pro-inflammatory and anti-inflammatory compounds. Low-grade systemic inflammation occurs in clinical conditions such as insulin resistance, hypertension, type 2 diabetes mellitus, atherosclerosis, coronary heart disease, lupus, schizophrenia, Alzheimer's disease, and other dementias, cancer and non-alcoholic fatty liver disease (NAFLD) that are also characterized by an alteration in the metabolism of essential fatty acids in the form of excess production of pro-inflammatory eicosanoids and possibly, decreased synthesis and release of anti-inflammatory lipoxins, resolvins, protectins and maresins. We propose that low-grade systemic inflammation observed in these clinical conditions is due to an imbalance in the metabolism of essential fatty acids that is more in favour of pro-inflammatory molecules. In this context, transgenic fat-1 mouse that is designed to convert n-6 to n-3 fatty acids could form an ideal model to study the altered metabolism of essential fatty acids in the above mentioned conditions. It is envisaged that low-grade systemic inflammatory conditions are much less likely in the fat-1 mouse and/or these diseases will run a relatively mild course. Identifying the anti-inflammatory compounds from n-3 fatty acids that suppress low-grade systemic inflammatory conditions and understanding their mechanism(s) of action may lead to newer therapeutic strategies.
Highlights
One traditional approach to modify tissue nutrient composition to study the effects of different diets is by supplementing the experimental groups with different diets consisting of many variations
We propose that the beneficial actions seen in transgenic fat1 mouse with regard to less severe colitis, chemicalinduced hepatitis, osteoporosis and anti-cancer activity are all due to enhanced formation of lipoxins, resolvins, protectins and maresins derived from Z-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)
We propose that the beneficial actions seen in transgenic fat-1 mouse with regard to less severe colitis, chemical-induced hepatitis and osteoporosis are due to enhanced formation of lipoxins, resolvins, protectins and maresins derived from Z-3 EPA and DHA
Summary
One traditional approach to modify tissue nutrient composition to study the effects of different diets is by supplementing the experimental groups with different diets consisting of many variations. The beneficial action of EPA and DHA in Alzheimer's disease, schizophrenia and dementia can be attributed to the formation of anti-inflammatory compounds such as lipoxins, resolvins, protectins and maresins from EPA and DHA Based on these evidences, we propose that in transgenic fat-1 mouse will have increased amounts of EPA and DHA in the brain and other tissues and plasma and show reduced activity of HMG-CoA reductase enzyme, altered SREBP-mediated gene transcription, decreased Ras activity and enhanced levels of various BMPs in the brain
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