dc.contributor.advisor |
Associate Professor Bernhard H. Breier |
en |
dc.contributor.advisor |
Associate Professor Marie Dziadek |
en |
dc.contributor.author |
Krechowec, Stefan Ostap |
en |
dc.date.accessioned |
2007-07-09T04:12:39Z |
en |
dc.date.available |
2007-07-09T04:12:39Z |
en |
dc.date.issued |
2007 |
en |
dc.identifier.citation |
Thesis (PhD--Paediatrics)--University of Auckland, 2007. |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/701 |
en |
dc.description.abstract |
The developmental origins of health and disease hypothesis suggests that exposure to adverse prenatal environmental influences can determine an individual’s susceptibility to obesity in adult life. However, the specific causal mechanisms which underlie this hypothesis have yet to be identified. Focusing on the potential mechanistic role of the leptin endocrine axis, the main objective of this thesis was to investigate the long term effects of prenatal undernutrition and different levels of postnatal nutrition on leptin sensitivity and the development of diet-induced obesity (DIO) in the Wistar rat.
A well established animal model of maternal undernutrition during pregnancy was used to induce prenatal undernutrition in experimental offspring. To investigate the interaction between prenatal nutrition and postnatal diet, and its effects on obesity development, female offspring were placed on three different diets: standard chow, a high fat diet or a calorie restricted diet. The effects of prenatal undernutrition and postnatal diet on leptin sensitivity were investigated, in adult offspring, by measuring the response to 14 days of peripheral leptin treatment. Changes in gene expression in the liver, retroperitoneal adipose tissue and soleus muscle were then characterised by custom microarray and quantitative real-time RT-PCR (QPCR) analysis.
Adult female offspring exposed to prenatal undernutrition (UN offspring) were found to exhibit leptin resistance in adulthood, independent of postnatal DIO. This result demonstrates for the first time that exposure to prenatal undernutrition has a long term effect on adult leptin sensitivity. In UN offspring fed on a high-fat diet, leptin resistance significantly accelerated the development of DIO while in contrast, offspring maintained on calorie restriction remained lean. These findings suggest that prenatal nutrition can shape future susceptibility to DIO by altering postnatal leptin sensitivity. An analysis of gene expression suggests that prenatal undernutrition causes the development of peripheral tissue-specific leptin resistance, and may also further enhance an offspring’s susceptibility to DIO by altering the regulation of peripheral tissue lipogenesis, mitochondrial function, glucocorticoid metabolism and insulin sensitivity.
In conclusion, these studies identify peripheral leptin resistance as a key mechanism that can influence postnatal susceptibility to DIO in female offspring exposed to prenatal undernutrition. Furthermore, the identification of specific changes in peripheral gene expression highlights four additional metabolic mechanisms which may also facilitate the development of DIO in leptin resistant UN offspring. |
en |
dc.language.iso |
en |
en |
dc.publisher |
ResearchSpace@Auckland |
en |
dc.relation.ispartof |
PhD Thesis - University of Auckland |
en |
dc.relation.isreferencedby |
UoA1724383 |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
Fetal programming |
en |
dc.subject |
Obesity |
en |
dc.subject |
Leptin |
en |
dc.title |
Prenatal and postnatal nutritional influences on leptin sensitivity and susceptibility to diet-induced obesity in the rat |
en |
dc.type |
Thesis |
en |
thesis.degree.discipline |
Paediatrics |
en |
thesis.degree.grantor |
The University of Auckland |
en |
thesis.degree.level |
Doctoral |
en |
thesis.degree.name |
PhD |
en |
dc.subject.marsden |
Fields of Research::320000 Medical and Health Sciences::321000 Clinical Sciences::321019 Paediatrics |
en |
dc.rights.holder |
Copyright: The author |
en |
pubs.local.anzsrc |
11 - Medical and Health Sciences |
en |
pubs.org-id |
Faculty of Medical & Hlth Sci |
en |
dc.identifier.wikidata |
Q112870395 |
|