TY - JOUR
T1 - Early life disruption to the ghrelin system with over-eating is resolved in adulthood in male rats
AU - Sominsky, Luba
AU - Ziko, Ilvana
AU - Nguyen, Thai-Xinh
AU - Andrews, Zane B.
AU - Spencer, Sarah J.
PY - 2017/2
Y1 - 2017/2
N2 - Early life overweight is a significant risk factor for developmental programming of adult obesity due to changes in the availability of metabolic factors crucial for the maturation of brain appetite-regulatory circuitry. The appetite-stimulating hormone, ghrelin, has been recently identified as a major regulator of the establishment of hypothalamic feeding pathways. Ghrelin exists in circulation in two major forms, as acylated and des-acylated ghrelin. While most research has focused on acyl ghrelin, the role of neonatal des-acyl ghrelin in metabolic programming is currently unknown. Here we assessed the influences of early life overfeeding on the ghrelin system, including acyl and des-acyl ghrelin’s ability to access the hypothalamus in male rats. Our data show that early life overfeeding influences the ghrelin system short-term, leading to an acute reduction in circulating des-acyl ghrelin and increased expression of the growth hormone secretagogue receptor (GHSR) in the arcuate nucleus of the hypothalamus (ARC). These changes are associated with increased neuronal activation in response to exogenous acyl, but not des-acyl, ghrelin in the ARC and the paraventricular nucleus of the hypothalamus (PVN). Interestingly, while we observed no differences in the accessibility of the ARC to acyl or des-acyl ghrelin, less exogenous acyl ghrelin reaches the PVN in the neonatally overfed. Importantly, the influences of neonatal overfeeding on the ghrelin system were not maintained into adulthood. Therefore, while early life overfeeding results in excess body weight and stimulates acute changes in the brain's sensitivity to metabolic signals, this developmental mal-programming is at least partially alleviated in adulthood.
AB - Early life overweight is a significant risk factor for developmental programming of adult obesity due to changes in the availability of metabolic factors crucial for the maturation of brain appetite-regulatory circuitry. The appetite-stimulating hormone, ghrelin, has been recently identified as a major regulator of the establishment of hypothalamic feeding pathways. Ghrelin exists in circulation in two major forms, as acylated and des-acylated ghrelin. While most research has focused on acyl ghrelin, the role of neonatal des-acyl ghrelin in metabolic programming is currently unknown. Here we assessed the influences of early life overfeeding on the ghrelin system, including acyl and des-acyl ghrelin’s ability to access the hypothalamus in male rats. Our data show that early life overfeeding influences the ghrelin system short-term, leading to an acute reduction in circulating des-acyl ghrelin and increased expression of the growth hormone secretagogue receptor (GHSR) in the arcuate nucleus of the hypothalamus (ARC). These changes are associated with increased neuronal activation in response to exogenous acyl, but not des-acyl, ghrelin in the ARC and the paraventricular nucleus of the hypothalamus (PVN). Interestingly, while we observed no differences in the accessibility of the ARC to acyl or des-acyl ghrelin, less exogenous acyl ghrelin reaches the PVN in the neonatally overfed. Importantly, the influences of neonatal overfeeding on the ghrelin system were not maintained into adulthood. Therefore, while early life overfeeding results in excess body weight and stimulates acute changes in the brain's sensitivity to metabolic signals, this developmental mal-programming is at least partially alleviated in adulthood.
KW - Feeding
KW - Fluorescently-labelled ghrelin
KW - Metabolism
KW - Obesity
KW - Perinatal programming
UR - http://www.scopus.com/inward/record.url?scp=84989189614&partnerID=8YFLogxK
U2 - 10.1016/j.neuropharm.2016.09.023
DO - 10.1016/j.neuropharm.2016.09.023
M3 - Article
AN - SCOPUS:84989189614
VL - 113
SP - 21
EP - 30
JO - Neuropharmacology
JF - Neuropharmacology
SN - 0028-3908
IS - Part A
ER -