Postnatal diet-induced obesity in rats upregulates systemic and adipose tissue glucocorticoid metabolism during development and in adulthood: its relationship with the metabolic syndrome.
In humans, a hyperactivity of glucocorticoid metabolism was postulated to be involved in the intrauterine programming of the metabolic syndrome in adulthood. We studied in rats the effects of overfeeding, obtained by reducing the size of the litter in the immediate postnatal period, a time crucial for neuroendocrine maturation such as late gestation in humans. Overfeeding induced early-onset obesity and accelerated the maturation of the hypothalamo-pituitary-adrenal (HPA) axis together with an upregulation of adipose tissue glucocorticoid receptor (GR) mRNA. In adulthood, neonatally overfed rats presented with moderate increases in basal and stress-induced corticosterone secretion and striking changes in visceral adipose tissue glucocorticoid signaling, that is, enhanced GR and 11beta-hydroxysteroid dehydrogenase type 1 mRNA levels. The above-mentioned alterations in the endocrine status of overfed rats were accompanied by a moderate overweight status and significant metabolic disturbances comparable to those described in the metabolic syndrome. Our data demonstrate for the first time that postnatal overfeeding accelerates the maturation of the HPA axis and leads to permanent upregulation of the HPA axis and increased adipose tissue glucocorticoid sensitivity. Thus, the experimental paradigm of postnatal overfeeding is a powerful tool to understand the pathophysiology of glucocorticoid-induced programming of metabolic axes.
Boullu-Ciocca
Sandrine
S
Laboratoire d'Hématologie, INSERM UMR 626, Faculté de Médecine, 27 Bd Jean Moulin, 13385 Marseille Cedex 5, France.
Dutour
Anne
A
Guillaume
Viviane
V
Achard
Vincent
V
Oliver
Charles
C
Grino
Michel
M
D000273:Adipose Tissue / Q000254:growth & development* / Q000378:metabolism*; D000375:Aging / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology*; D004032:Diet; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005938:Glucocorticoids / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D024821:Metabolic Syndrome / Q000209:etiology; D009765:Obesity / Q000209:etiology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D014886:Weaning
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D005938:Glucocorticoids; D007328:Insulin; D020738:Leptin