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Title: A comparison of the physiological and molecular effects of short term starvation and long term caloric restriction
Author: Sinclair, Rachel Elizabeth
ISNI:       0000 0004 2745 917X
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2013
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Currently, we are experiencing a global epidemic of obesity and its associated comorbidities, such as hypertension, diabetes and certain types of cancer, which in turn create a great burden on healthcare resources. Obesity is the result of an imbalance between energy intake and energy expenditure, therefore understanding mechanisms which regulate energy balance and body mass are crucial in order to prevent and treat obesity. To better understand the regulation of body mass and energy intake, two dietary intervention regimes were investigated: an acute starvation experiment and long term caloric restriction. Daily fluctuations in energy intake and energy expenditure and their impact on weight changes are not closely linked over the short term in un-manipulated circumstances; therefore this suggests that the simple set point model of body mass regulation is not accurate. The dual intervention point model provides a useful alternative to the set-point idea, and provides a conceptual basis for understanding why such parameters would not be associated in day to day measurements of un-manipulated animals. As predicted from this model more extreme manipulations - specifically 24h starvation and 29 days of restricted energy intake by 30% - caused animals to enable a series of compensatory responses that were similar but not identical. In particular these included elevation of daytime activity, and a strong hyperphagia following restoration of food supply that lasted up to 4 days but was restricted to the night time. It was found that NPY changes probably did not underpin the post restriction hyperphagia but that changes in AgRP and POMC were probably more 8 significant. Peripheral signals including leptin, insulin and TNFα are also important in relaying the peripheral status to the brain. Data suggested that TNFαR1 is critical to mediating the physical activity changes in both 24h and prolonged CR and the level of hyperphagia. In summary, this work has generated novel information on physiological, behavioural and molecular cues of body mass regulation, which contributes to a better understanding and provides useful insights for the prevention and treatment of obesity.
Supervisor: Not available Sponsor: Biotechnology and Biological Sciences Research Council (Great Britain) ; Pfizer Inc
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available