PURPOSE: Early weaning (EW) is a stressful condition that programmes a child to be overweight in adult life. Fat mass depends on glucocorticoids (GC) to regulate adipogenesis and lipogenesis. We hypothesised that the increased adiposity in models of EW was due to a disturbed HPA axis and/or disrupted GC function. METHODS: We used two experimental models, pharmacological early weaning (PEW, dams were bromocriptine-treated) and non-pharmacological early weaning (NPEW, dams' teats were wrapped with a bandage), which were initiated during the last 3 days of lactation. Offspring from both genders was analysed on postnatal day 180. RESULTS: Offspring in both models were overweight with increased visceral fat mass, but plasma corticosterone was increased in both genders in the PEW group but not the NPEW group. NPEW males had increased GRα expression in visceral adipose tissue (VAT), and GRα expression decreased in PEW males in subcutaneous adipose tissue (SAT). Females in both EW groups had increased 11βHSD1 expression in SAT. PEW males had increased C/EBPβ expression in SAT. PEW females had lower PPARy and FAS expression in VAT than the NPEW females. We detected a sex dimorphism in VAT and SAT in the EW groups regarding 11βHSD1, GRα and C/EBPβ expression. CONCLUSIONS: The accumulated adiposity induced by EW exhibited distinct mechanisms depending on gender, specific fat deposition and GC metabolism and action. The higher proportion of VAT/SAT in both sets of EW males may be related to the action of GC in these tissues, and the higher conversion of GC in SAT in females may explain the differences in the fat distribution.
PURPOSE: Early weaning (EW) is a stressful condition that programmes a child to be overweight in adult life. Fat mass depends on glucocorticoids (GC) to regulate adipogenesis and lipogenesis. We hypothesised that the increased adiposity in models of EW was due to a disturbed HPA axis and/or disrupted GC function. METHODS: We used two experimental models, pharmacological early weaning (PEW, dams were bromocriptine-treated) and non-pharmacological early weaning (NPEW, dams' teats were wrapped with a bandage), which were initiated during the last 3 days of lactation. Offspring from both genders was analysed on postnatal day 180. RESULTS: Offspring in both models were overweight with increased visceral fat mass, but plasma corticosterone was increased in both genders in the PEW group but not the NPEW group. NPEW males had increased GRα expression in visceral adipose tissue (VAT), and GRα expression decreased in PEW males in subcutaneous adipose tissue (SAT). Females in both EW groups had increased 11βHSD1 expression in SAT. PEW males had increased C/EBPβ expression in SAT. PEW females had lower PPARy and FAS expression in VAT than the NPEW females. We detected a sex dimorphism in VAT and SAT in the EW groups regarding 11βHSD1, GRα and C/EBPβ expression. CONCLUSIONS: The accumulated adiposity induced by EW exhibited distinct mechanisms depending on gender, specific fat deposition and GC metabolism and action. The higher proportion of VAT/SAT in both sets of EW males may be related to the action of GC in these tissues, and the higher conversion of GC in SAT in females may explain the differences in the fat distribution.
Entities:
Keywords:
Adipogenesis and lipogenesis; Early weaning; Glucocorticoids
Authors: Marie-Soleil Gauthier; Joelle R Pérusse; Marie-Ève Lavoie; Robert Sladek; S R Murthy Madiraju; Neil B Ruderman; Benoit Coulombe; Marc Prentki; Rémi Rabasa-Lhoret Journal: J Clin Endocrinol Metab Date: 2014-12 Impact factor: 5.958