TY - JOUR
T1 - Neonatal overfeeding increases capacity for catecholamine biosynthesis from the adrenal gland acutely and long-term in the male rat
AU - Sominsky, Luba
AU - Ong, Lin Kooi
AU - Ziko, Ilvana
AU - Dickson, Phillip W.
AU - Spencer, Sarah J.
N1 - Funding Information:
LS is an RMIT University VC Postdoctoral Research Fellow. SJS is funded by a National Health and Medical Research Council Career Development Fellowship (APP1128646) and a Brain Foundation Research Gift. LKO and PWD are funded by Hunter Medical Research Institute and Faculty of Health and Medicine Pilot Grant, The University of Newcastle, Australia.
Funding Information:
LS is an RMIT University VC Postdoctoral Research Fellow. SJS is funded by a National Health and Medical Research Council Career Development Fellowship ( APP1128646 ) and a Brain Foundation Research Gift. LKO and PWD are funded by Hunter Medical Research Institute and Faculty of Health and Medicine Pilot Grant, The University of Newcastle, Australia .
Publisher Copyright:
© 2017 Elsevier B.V.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2018/7/15
Y1 - 2018/7/15
N2 - A poor nutritional environment during early development has long been known to increase disease susceptibility later in life. We have previously shown that rats that are overfed as neonates (i.e. suckled in small litters (4 pups) relative to control conditions (12 pups)) show dysregulated hypothalamic-pituitary-adrenal axis responses to immune stress in adulthood, particularly due to an altered capacity of the adrenal to respond to an immune challenge. Here we hypothesised that neonatal overfeeding similarly affects the sympathomedullary system, testing this by investigating the biochemical function of tyrosine hydroxylase (TH), the first rate-limiting enzyme in the catecholamine synthesis. We also examined changes in adrenal expression of the leptin receptor and in mitogen-activated protein kinase (MAPK) signalling. During the neonatal period, we saw age-dependent changes in TH activity and phosphorylation, with neonatal overfeeding stimulating increased adrenal TH specific activity at postnatal days 7 and 14, along with a compensatory reduction in total TH protein levels. This increased TH activity was maintained into adulthood where neonatally overfed rats exhibited increased adrenal responsiveness 30 min after an immune challenge with lipopolysaccharide, evident in a concomitant increase in TH protein levels and specific activity. Neonatal overfeeding significantly reduced the expression of the leptin receptor in neonatal adrenals at postnatal day 7 and in adult adrenals, but did not affect MAPK signalling. These data suggest neonatal overfeeding alters the capacity of the adrenal to synthesise catecholamines, both acutely and long term, and these effects may be independent of leptin signalling.
AB - A poor nutritional environment during early development has long been known to increase disease susceptibility later in life. We have previously shown that rats that are overfed as neonates (i.e. suckled in small litters (4 pups) relative to control conditions (12 pups)) show dysregulated hypothalamic-pituitary-adrenal axis responses to immune stress in adulthood, particularly due to an altered capacity of the adrenal to respond to an immune challenge. Here we hypothesised that neonatal overfeeding similarly affects the sympathomedullary system, testing this by investigating the biochemical function of tyrosine hydroxylase (TH), the first rate-limiting enzyme in the catecholamine synthesis. We also examined changes in adrenal expression of the leptin receptor and in mitogen-activated protein kinase (MAPK) signalling. During the neonatal period, we saw age-dependent changes in TH activity and phosphorylation, with neonatal overfeeding stimulating increased adrenal TH specific activity at postnatal days 7 and 14, along with a compensatory reduction in total TH protein levels. This increased TH activity was maintained into adulthood where neonatally overfed rats exhibited increased adrenal responsiveness 30 min after an immune challenge with lipopolysaccharide, evident in a concomitant increase in TH protein levels and specific activity. Neonatal overfeeding significantly reduced the expression of the leptin receptor in neonatal adrenals at postnatal day 7 and in adult adrenals, but did not affect MAPK signalling. These data suggest neonatal overfeeding alters the capacity of the adrenal to synthesise catecholamines, both acutely and long term, and these effects may be independent of leptin signalling.
KW - Development
KW - Nutrition
KW - Obesity
KW - Stress
KW - Tyrosine hydroxylase
UR - http://www.scopus.com/inward/record.url?scp=85035207152&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2017.11.014
DO - 10.1016/j.mce.2017.11.014
M3 - Article
C2 - 29183807
AN - SCOPUS:85035207152
SN - 0303-7207
VL - 470
SP - 295
EP - 303
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
ER -