title: Rescue of glucocorticoid-programmed adipocyte inflammation by omega-3 fatty acid supplementation in the rat.
abstract: BACKGROUND
  Adverse fetal environments predispose offspring to pathologies associated with the metabolic syndrome. Previously we demonstrated that adult offspring of dexamethasone-treated mothers had elevated plasma insulin and pro-inflammatory cytokines, effects prevented by a postnatal diet enriched with omega (n)-3 fatty acids. Here we tested whether prenatal glucocorticoid excess also programmed the adipose tissue phenotype, and whether this outcome is rescued by dietary n-3 fatty acids.
  
  
  METHODS
  Offspring of control and dexamethasone-treated mothers (0.75 μg/ml in drinking water, day 13 to term) were cross-fostered to mothers on a standard (Std) or high n-3 (Hn3) diet at birth. Offspring remained on these diets post-weaning, and serum and retroperitoneal fat were obtained at 6 months of age (n = 5-8 per group). Serum was analysed for blood lipids and fatty acid profiles, adipocyte cross sectional area was measured by unbiased stereological analysis and adipose expression of markers of inflammation, glucocorticoid sensitivity and lipid metabolism were determined by RT-qPCR analysis.
  
  
  RESULTS
  Serum total fatty acid levels were elevated (P < 0.01) in male offspring of dexamethasone-treated mothers, an effect prevented by Hn3 consumption. Prenatal dexamethasone also programmed increased adipose expression of Il6, Il1b (both P < 0.05) and Tnfa (P < 0.001) mRNAs regardless of fetal sex, but again this effect was prevented (for Il6 and Il1b) by Hn3 consumption. Offspring of dexamethasone-treated mothers had increased adipose expression of Gr (P = 0.008) and Ppara (P < 0.05) regardless of sex or postnatal diet, while 11bHsd1 was upregulated in males only. The Hn3 diet increased Ppard expression and reduced adipocyte size in all offspring (both P < 0.05) irrespective of prenatal treatment.
  
  
  CONCLUSIONS
  Prenatal glucocorticoid exposure programmed increased expression of inflammatory markers and enhanced glucocorticoid sensitivity of adipose tissue. Partial prevention of this phenotype by high n-3 consumption indicates that postnatal dietary manipulations can limit adverse fetal programming effects on adipose tissue.
authors.affiliation: School of Anatomy, Physiology & Human Biology, The University of Western Australia, Perth, Australia. peter.mark@uwa.edu.au.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Mark
authors.forename: Caitlin S
authors.initials: CS
authors.lastname: Wyrwoll
authors.forename: Intan S
authors.initials: IS
authors.lastname: Zulkafli
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Mori
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Waddell
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003907:Dexamethasone / Q000031:analogs & derivatives; D019587:Dietary Supplements; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D047109:Fetal Development; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007774:Lactation; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D024821:Metabolic Syndrome / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology*; D011897:Random Allocation; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological / Q000503:physiopathology*; D015854:Up-Regulation; D014886:Weaning
chemical_list: D015525:Fatty Acids, Omega-3; D018836:Inflammation Mediators; C542344:NR3C1 protein, rat; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; C018038:dexamethasone acetate; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1