Postnatal programming of glucocorticoid metabolism in rats modulates high-fat diet-induced regulation of visceral adipose tissue glucocorticoid exposure and sensitivity, and adiponectin and pro-inflammatory adipokines gene expression in adulthood.

Abstract

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 (AT) glucocorticoid metabolism (11β-hydroxysteroid dehydrogenase type 1 [11β-HSD-1]-induced corticosterone reactivation). We hypothesized that postnatal programming could modulate high-fat diet-induced AT dysregulation in adulthood.

Research Design and Methods: We compared the effects of chronic (from weaning on) 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 AT adiponectin. Both manipulations did not alter 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 AT (MAT) glucocorticoid sensitivity and triggered high-fat diet-induced increase in MAT glucocorticoid exposure, subsequent to enhanced MAT 11β-HSD-1 gene expression. MAT tumor necrosis factor (TNF) α, TNF-Receptor 1, IL6, 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, this effect being further enhanced by high-fat diet for TNFα and IL6.

Conclusions: Our data show for the first time that a postnatal manipulation programs high-fat diet-induced up-regulation 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 AT dysregulation in adulthood. They also urge the need for clinical trials with specific 11β-HSD-1 inhibitors.