Postnatal programming of glucocorticoid metabolism in rats modulates high-fat diet-induced regulation of visceral adipose tissue glucocorticoid exposure and sensitivity and adiponectin and proinflammatory adipokines gene expression in adulthood.
OBJECTIVE
Alterations of the perinatal environment, which lead to increased prevalence of the metabolic syndrome in adulthood, program an upregulation of systemic and/or adipose tissue glucocorticoid metabolism (11 beta-hydroxysteroid dehydrogenase type 1 [11 beta-HSD-1]-induced corticosterone reactivation). We hypothesized that postnatal programming could modulate high-fat diet-induced adipose tissue dysregulation in adulthood.


METHODS
We compared the effects of chronic (since weaning) high- or low-fat diet in postnatally normofed (control) or overfed (programmed) rats.


RESULTS
Postnatal programming accentuated high-fat diet-induced overweight, insulin resistance, glucose intolerance, and decrease in circulating and epididymal adipose tissue adiponectin. Neither manipulation altered liver function. Postnatal programming or high-fat diet increased systemic corticosterone production, which was not further modified when both manipulations were associated. Postnatal programming suppressed high-fat diet-induced decrease in mesenteric adipose tissue (MAT) glucocorticoid sensitivity and triggered high-fat diet-induced increase in MAT glucocorticoid exposure, subsequent to enhanced MAT 11 beta-HSD-1 gene expression. MAT tumor necrosis factor (TNF)-alpha, TNF-receptor 1, interleukin (IL)-6, resistin, and plasminogen activator inhibitor-1 mRNAs were not changed by high-fat feeding in control rats and showed a large increase in programmed animals, with this effect further enhanced by high-fat diet for TNF-alpha and IL-6.


CONCLUSIONS
Our data show for the first time that postnatal manipulation programs high-fat diet-induced upregulation of MAT glucocorticoid exposure, sensitivity, and inflammatory status and therefore reveal the pivotal role of the environment during the perinatal period on the development of diet-induced adipose tissue dysregulation in adulthood. They also urge the need for clinical trials with specific 11 beta-HSD-1 inhibitors.
INSERM U626, Faculté de Médecine, 27 Bd Jean Moulin, 13385 Marseille Cedex 5, France.
Sandrine
S
Boullu-Ciocca
Vincent
V
Achard
Virginie
V
Tassistro
Anne
A
Dutour
Michel
M
Grino
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism; D054392:Adipokines / Q000235:genetics / Q000378:metabolism*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000375:Aging; D000818:Animals; D003345:Corticosterone / Q000378:metabolism / Q000652:urine; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology*; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000378:metabolism*; D018149:Glucose Intolerance; D007249:Inflammation; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D050177:Overweight; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D054392:Adipokines; D052242:Adiponectin; D004041:Dietary Fats; D005938:Glucocorticoids; D047495:PPAR gamma; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D003345:Corticosterone