RT Journal Article
T1 Early overnutrition sensitizes the growth hormone axis to the impact of diet-induced obesity via sex-divergent mechanisms
A1 Sanchez-Garrido, M.A.
A1 Ruiz-Pino, F.
A1 Pozo-Salas, A.I.
A1 Castellano, J.M.
A1 Vazquez, M.J.
A1 Luque, R.M.
A1 Tena-Sempere, M.
K1 Overnutrition
K1 Obesity
K1 Growth hormone
K1 Sex characteristics
K1 Hipernutrición
K1 Obesidad
K1 Hormona del crecimiento
K1 Características sexuales
K1 Metabolismo
AB In addition to its essential role in the physiological control of longitudinal growth, growth-hormone (GH) is endowed with relevant metabolic functions, including anabolic actions in muscle, lipolysis in adipose-tissue and glycemic modulation. Adult obesity is known to negatively impact GH-axis, thereby promoting a vicious circle that may contribute to the exacerbation of the metabolic complications of overweight. Yet, to what extent early-overnutrition sensitizes the somatotropic-axis to the deleterious effects of obesity remains largely unexplored. Using a rat-model of sequential exposure to obesogenic insults, namely postnatal-overfeeding during lactation and high-fat diet (HFD) after weaning, we evaluated in both sexes the individual and combined impact of these nutritional challenges upon key elements of the somatotropic-axis. While feeding HFD per se had a modest impact on the adult GH-axis, early overnutrition had durable effects on key elements of the somatotropic-system, which were sexually different, with a significant inhibition of pituitary gene expression of GH-releasing hormone-receptor (GHRH-R) and somatostatin receptor-5 (SST5) in males, but an increase in pituitary GHRH-R, SST2, SST5, GH secretagogue-receptor (GHS-R) and ghrelin expression in females. Notably, early-overnutrition sensitized the GH-axis to the deleterious impact of HFD, with a significant suppression of pituitary GH expression in both sexes and lowering of circulating GH levels in females. Yet, despite their similar metabolic perturbations, males and females displayed rather distinct alterations of key somatotropic-regulators/ mediators. Our data document a synergistic effect of postnatal-overnutrition on the detrimental impact of HFD-induced obesity on key elements of the adult GH-axis, which is conducted via mechanisms that are sexually-divergent.
PB Springer Nature
YR 2020
FD 2020-08-17
LK http://hdl.handle.net/10668/3890
UL http://hdl.handle.net/10668/3890
LA en
NO Sanchez-Garrido MA, Ruiz-Pino F, Pozo-Salas AI, Castellano JM, Vazquez MJ, Luque RM, et al. Early overnutrition sensitizes the growth hormone axis to the impact of diet-induced obesity via sex-divergent mechanisms. Sci Rep. 2020 Aug 17;10(1):13898
DS RISalud
RD Apr 18, 2025