| Abstract No.: | C-E3160 |
| Country: | Canada |
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| Title: | MODULATION OF THE NEONATAL STRESS RESPONSE AND METABOLIC PROFILE BY PERINATAL FAT INTAKE AND PARTICIPATION OF THE ENDOCANNABINOID SYSTEM |
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| Authors/Affiliations: | 2 Esterina D'Asti*; 2 Hong Long; 1 Jennifer Tremblay Mercier; 1 Stephen Cunnane; 2 Claire Dominique Walker;
1 Centre de Recherche sur le Vieillissement, Sherbrooke, QC, Canada; 2 Douglas Mental Health University Institute, Montreal, QC, Canada
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| Content: | Studies have implicated endocannabinoids (eCBs), products of phospholipid (PL) metabolism, in the regulation of numerous physiological and behavioral processes including responses to stress. Previously, we found that neonatal rats feeding on high fat milk display reduced stress responsiveness. Objectives: we hypothesize that manipulation of the neonatal phospholipid (PL) fatty acid (FA) content of the brain affects the neonatal stress response via alterations in the production of eCBs in stress-activated areas. Methods: dams were fed a low (C), or high fat diet rich in either n-6 (hydrogenated vegetable oil, HF) or n-3 (fish oil, HFF) polyunsaturated fat during the last week of gestation and through lactation. Offspring were weaned on the same diet as their mother. In the first experiment, the plasma and brains of pups were collected on PND10 and 34 for baseline hormonal (insulin; leptin; corticosterone, CORT) as well as PL FA and eCB content analysis. In the second experiment, we tested the effect of pretreatment with either saline, or a CB1 receptor antagonist (AM251, 1 or 3 mg/kg bw, ip) on the hormonal stress response in PND10 pups from each diet group. Results: on PND10, the high fat groups tended to have greater plasma levels of CORT and insulin than C pups while leptin was significantly elevated only in the HF group compared to C and HFF offspring (HFF>C). In addition, the HF group displayed a significantly greater retroperitoneal fat pad weight compared to the C group, which was similar to HFF pups. After weaning, PND34 high fat-fed offspring tended to have elevated levels of leptin relative to C pups whereas each diet group demonstrated comparable fat pad weights. Furthermore, all diet groups exhibited comparable CORT levels, and C offspring displayed a significantly higher level of insulin relative to HFF pups (HF>HFF). Thus the nature of maternal dietary fat can influence hormones known to affect stress responsiveness and eCB levels in young pups. We are currently examining diet-induced changes in tissue eCBs and PL FAs. Importantly, eCBs may regulate the stress response in neonates since on PND10 the CB1R antagonist dose-dependently increased the peak ACTH response to ether stress in C offspring. The HF and HFF groups tended to be mildly sensitive or insensitive to the antagonist, respectively. Since HFF pups exhibited significantly greater CORT levels relative to C and HF offspring (HF>C) after stress, we suggest that an increased glucocorticoid negative feedback response in this group might be responsible for blunted ACTH secretion. Conclusions: These results suggest that 1) the nature of the maternal dietary fat determines different metabolic hormonal profiles in the offspring and 2) eCBs may occupy a more prominent role in reducing stress responsiveness in neonatal rats fed a low fat diet compared to a high fat diet. Supported by NSERC.
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