High dietary omega-6 fatty acids contribute to reduced docosahexaenoic acid in the developing brain and inhibit secondary neurite growth.
Docosahexaenoic acid (DHA, 22:6omega-3) is a major polyunsaturated fatty acid in the brain and is required in large amounts during development. Low levels of DHA in the brain are associated with functional deficits. The omega-3 fatty acids are essential nutrients and their metabolism and incorporation in developing brain depends on the composition of dietary fat. We assessed the importance of the intake of the omega-3 fatty acid, 18:3omega-3 and the balance with the omega-6 fatty acid, 18:2omega-6, and the effects of dietary arachidonic acid (20:4omega-6) and DHA in milk diets using the piglet as a model of early infant nutrition. Piglets were fed (% energy) 1.2% 18:2omega-6 and 0.05% 18:3omega-3 (deficient), 10.7% 18:2omega-6 and 1.1% 18:3omega-3 (contemporary), 1.2% 18:2omega-6 and 1.1% 18:3omega-3 (evolutionary), or the contemporary diet with 0.3% 20:4omega-6 and 0.3% DHA (supplemented) from birth to 30 days of age. Our results show that a contemporary diet, high in 18:2omega-6 compromises DHA accretion and leads to increased 22:4omega-6 and 22:5omega-6 in the brain. However, an evolutionary diet, low in 18:2omega-6, supports high brain DHA. DHA supplementation effectively increased DHA, but not the intermediate omega-3 fatty acids, 20:5omega-3 and 22:5omega-3. Using primary cultures of cortical neurons, we show that 22:5omega-6 is efficiently acylated and preferentially taken up over DHA. However, DHA, but not 22:5omega-6 supports growth of secondary neurites. Our results suggest the need to consider whether current high dietary omega-6 fatty acid intakes compromise brain DHA accretion and contribute to poor neurodevelopment.
Novak
Elizabeth M
EM
Nutrition Research Program, Child and Family Research Institute, Department of Paediatrics, University of British Columbia, Vancouver, B.C., Canada.
Dyer
Roger A
RA
Innis
Sheila M
SM
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D016718:Arachidonic Acid; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage*; D008297:Male; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000166:cytology; D013552:Swine; D014018:Tissue Distribution
D043371:Fatty Acids, Omega-6; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid