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Title: The role of early life nutrition and leptin in the programming of energy balance
Author: Cottrell, E. C.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2009
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To better understand the development of energy balance systems in the postnatal rat and the role of leptin, gene expression of leptin receptors (ObR) and energy balance neuropeptides in the hypothalamus were measured using in situ hybridisation, along with endogenous leptin concentrations over the lactation period. Expression of ObR and both orexigenic and anorexigenic neuropeptides increased in the arcuate nucleus over the lactation period. In addition, at postnatal day 4 (P4), dense ObR expression was detected in ependymal cells of the third ventricle (3V) but disappeared at later postnatal ages. An acute leptin challenge robustly induced suppressor of cytokine signalling-3 (SOCS-3) expression in the 3V of P4 but not P14 animals, revealing developmental changes in the site of leptin action and suggesting that 3V leptin receptors may mediate in part the accounts of leptin in the early postnatal period. Manipulation of early nutrition was used to study the effects of fetal growth restriction followed by rapid postnatal growth (‘recuperated’ offspring) and of slow growth during the lactation period (‘postnatal low protein offspring’). The feeding of either a control or low protein diet during gestation and lactation, cross fostering and litter size manipulation had a marked effect on the leptin profile in neonatal rats, but differences in hypothalamic gene expression between groups were not observed until the end of the second postnatal week. In mice, the postnatal hypothalamic neuropeptide profiles were found to differ markedly from the rat. However, like the rat, there was a progressive increase in leptin receptor over the lactation period. Leptin replacement in early life in ob/ob mice was unable to modify the development of obesity in these animals.  These findings indicated that although there may be a critical window in which leptin can rescue certain aspects of hypothalamic development, this hormone is required in an ongoing manner for regulation of body weight in the adult.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available