Prenatal and postnatal nutritional influences on leptin sensitivity and susceptibility to diet-induced obesity in the rat

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dc.contributor.advisor Associate Professor Bernhard H. Breier en
dc.contributor.advisor Associate Professor Marie Dziadek en Krechowec, Stefan Ostap en 2007-07-09T04:12:39Z en 2007-07-09T04:12:39Z en 2007 en
dc.identifier.citation Thesis (PhD--Paediatrics)--University of Auckland, 2007. en
dc.identifier.uri 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 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 Paediatrics en The University of Auckland en Doctoral en 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 Faculty of Medical & Hlth Sci en
dc.identifier.wikidata Q112870395

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