Dietary n-3 long chain PUFA supplementation promotes a pro-resolving oxylipin profile in the brain |
| |
| Institution: | 1. Department of Food and Human Nutritional Sciences, University of Manitoba, Canada;2. Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, Canada;3. School of Medicine, Federal University of Uberlândia, Brazil;4. Department of Physiology and Pathophysiology, University of Manitoba, Canada;1. Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA;2. National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA;3. FOODplus Research Center, School of Agriculture, Food and Wine, The University of Adelaide, Adelaide, Australia;4. Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California, Davis, CA, USA;5. Department of Pediatrics, University of California, San Diego, CA, USA;6. School of Medicine, University of Louisville, Louisville, KY, USA;7. Neurobiology Section, Center for Neural Circuits and Behavior, Department of Neurosciences, University of California, San Diego, USA;8. South Australian Health and Medical Research Institute, Adelaide, Australia;1. Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan;2. Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka, Bangladesh;3. Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama-City, Kanagawa 230-0045, Japan |
| |
| Abstract: | The brain is highly enriched in long chain polyunsaturated fatty acids (LC-PUFAs) that display immunomodulatory properties in the brain. At the periphery, the modulation of inflammation by LC-PUFAs occurs through lipid mediators called oxylipins which have anti-inflammatory and pro-resolving activities when derived from n-3 LC-PUFAs and pro-inflammatory activities when derived from n-6 LC-PUFAs. However, whether a diet rich in LC-PUFAs modulates oxylipins and neuroinflammation in the brain has been poorly investigated. In this study, the effect of a dietary n-3 LC-PUFA supplementation on oxylipin profile and neuroinflammation in the brain was analyzed. Mice were given diets deficient or supplemented in n-3 LC-PUFAs for a 2-month period starting at post-natal day 21, followed by a peripheral administration of lipopolysaccharide (LPS) at adulthood. We first showed that dietary n-3 LC-PUFA supplementation induced n-3 LC-PUFA enrichment in the hippocampus and subsequently an increase in n-3 PUFA-derived oxylipins and a decrease in n-6 PUFA-derived oxylipins. In response to LPS, n-3 LC-PUFA deficient mice presented a pro-inflammatory oxylipin profile whereas n-3 LC-PUFA supplemented mice displayed an anti-inflammatory oxylipin profile in the hippocampus. Accordingly, the expression of cyclooxygenase-2 and 5-lipoxygenase, the enzymes implicated in pro- and anti-inflammatory oxylipin synthesis, was induced by LPS in both diets. In addition, LPS-induced pro-inflammatory cytokine increase was reduced by dietary n-3 LC-PUFA supplementation. These results indicate that brain n-3 LC-PUFAs increase by dietary means and promote the synthesis of anti-inflammatory derived bioactive oxylipins. As neuroinflammation plays a key role in all brain injuries and many neurodegenerative disorders, the present data suggest that dietary habits may be an important regulator of brain cytokine production in these contexts. |
| |
| Keywords: | Oxylipin Neuroinflammation N-3 PUFA DHA EPA 18-HEPE TxB2 EET |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
