Maternal dietary fat intake alters the neonatal stress response and metabolic profile in the offspring : participation of the endocannabinoid system?

Endocannabinoids are products of phospholipid-derived arachidonic acid that regulate hypothalamus-pituitary-adrenal axis activity. We hypothesize that differences in the quality and quantity of maternal dietary fat will modulate the neonatal phospholipid arachidonic acid content of the brain affecting the stress response via differences in endocannabinoid concentration of stress-activated brain areas. Dams were fed a 5% (C) or 300.10 fat diet rich in either n-6 (C, HF) or n-3 (HFF) fat during the perinatal period. PND4-5 HFF milk displays a reduced n-6/n-3 ratio compared to C and HF milk. PND10 hypothalamic and hippocampal PL AA levels are reduced in HFF pups relative to C and HF offspring; and predict endocannabinoid levels in a region-specific manner. In all pups pre-treated with an endocannabinoid receptor antagonist (AM251) or an inhibitor of the endocannabinoid degradative enzyme (URB597), basal and stress-induced ACTH secretion dose-dependently increased. Moreover, HFF pups exhibited a tendency towards reduced AM251 sensitivity under stressful conditions. These data suggest that the nature of perinatal dietary fat can differentially influence neonatal brain arachidonic acid levels and their endocannabinoid derivatives; and endocannabinoid signaling may be altered between diet groups since pups exhibit differences in sensitivity to endocannabinoid receptor blockade