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Title: Investigating the neuroendocrine control of metabolism and energy homeostasis
Author: Izzi-Engbeaya, Chioma Nmereobasi
ISNI:       0000 0004 9350 4223
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2018
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Obesity and associated metabolic disorders are major causes of morbidity and mortality in both developed and developing countries, but the options for treating these conditions are limited. Energy homeostasis and metabolism are regulated by a complex network of neuroendocrine systems, neural pathways, peripheral signals and circuits. Consequently, our knowledge of the regulation of energy homeostasis and metabolism remains incomplete. Two neuroendocrine systems were examined in this thesis, one involving glucocorticoids (a peripherally produced hormone acting centrally) and one involving kisspeptin (a centrally produced hormone acting peripherally). Reduction of active glucocorticoids in the arcuate nucleus of post-pubertal male rats (via stereotactic injection of recombinant adeno-associated virus to reduce expression of 11βHSD1) resulted in less weight gain despite matched food intake to controls on normal chow diet, with higher brown adipose tissue weight. However, on a high fat diet, reduction in arcuate active glucocorticoids resulted in higher average daily food intake and a trend towards higher body weight than controls. No differences in body composition, plasma corticosterone, plasma insulin and plasma glucose were produced by reduction of arcuate glucocorticoids. Administration of kisspeptin to healthy men resulted in increased glucose-stimulated insulin secretion (GSIS) during hyperglycaemia but not during euglycaemia. Kisspeptin enhanced GSIS without affecting the levels of metabolically active gut hormones. Additionally, acute kisspeptin administration did not affect appetite and food intake in healthy men. These results provide further insights into the neuroendocrine control of energy homeostasis and metabolism and may help guide the development of hormone-modulating therapies for the treatment of obesity and associated conditions.
Supervisor: Dhillo, Waljit ; Gardiner, James Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral