sominsky-hypothalamiceffectsof-2017.pdf (4.31 MB)
Hypothalamic effects of neonatal diet: reversible and only partially leptin dependent
journal contribution
posted on 2017-01-01, 00:00 authored by Luba SominskyLuba Sominsky, I Ziko, T X Nguyen, J Quach, S J SpencerEarly life diet influences metabolic programming, increasing the risk for long-lasting metabolic ill health. Neonatally overfed rats have an early increase in leptin that is maintained long term and is associated with a corresponding elevation in body weight. However, the immediate and long-term effects of neonatal overfeeding on hypothalamic anorexigenic pro-opiomelanocortin (POMC) and orexigenic agouti-related peptide (AgRP)/neuropeptide Y (NPY) circuitry, and if these are directly mediated by leptin, have not yet been examined. Here, we examined the effects of neonatal overfeeding on leptin-mediated development of hypothalamic POMC and AgRP/NPY neurons and whether these effects can be normalised by neonatal leptin antagonism in male Wistar rats. Neonatal overfeeding led to an acute (neonatal) resistance of hypothalamic neurons to exogenous leptin, but this leptin resistance was resolved by adulthood. While there were no effects of neonatal overfeeding on POMC immunoreactivity in neonates or adults, the neonatal overfeeding-induced early increase in arcuate nucleus (ARC) AgRP/NPY fibres was reversed by adulthood so that neonatally overfed adults had reduced NPY immunoreactivity in the ARC compared with controls, with no further differences in AgRP immunoreactivity. Short-term neonatal leptin antagonism did not reverse the excess body weight or hyperleptinaemia in the neonatally overfed, suggesting factors other than leptin may also contribute to the phenotype. Our findings show that changes in the availability of leptin during early life period influence the development of hypothalamic connectivity short term, but this is partly resolved by adulthood indicating an adaptation to the metabolic mal-programming effects of neonatal overfeeding.
History
Journal
The journal of endocrinologyVolume
234Issue
1Pagination
41 - 56Publisher
BioScientifica Ltd.Location
Bristol, Eng.Publisher DOI
ISSN
0022-0795eISSN
1479-6805Language
EnglishPublication classification
C1 Refereed article in a scholarly journalUsage metrics
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No categories selectedKeywords
agouti-related peptideAGOUTI-RELATED PROTEINARCUATE NUCLEUSBODY-WEIGHTdevelopmental programmingEndocrinology & MetabolismFEEDING-BEHAVIORLife Sciences & BiomedicineMATERNAL OBESITYneuropeptide YNEUROPEPTIDE-YobesityPARAVENTRICULAR NUCLEUSPOMC NEURONSPOSTNATAL LEPTINpro-opiomelanocortinPROOPIOMELANOCORTIN NEURONSScience & Technology
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