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Title: The role of amino acids in appetite regulation
Author: McGavigan, Anne
ISNI:       0000 0005 0732 0469
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2014
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There is currently a lack of safe and effective treatment options for obesity. A high protein diet is an effective weight loss and weight maintenance strategy. However, like many diets, high protein diets can be difficult to adhere to. The mechanisms by which protein exerts its weight-reducing effect remain unclear. However, it has been reported that different types of protein exert different effects on appetite. One possible explanation for these differences is the varied amino acid constituents of the protein. Preliminary data from our group investigated the effect of a range of amino acids on food intake in rodents. L-cysteine was identified as the most anorexigenic amino acid. This thesis has investigated the effect of L-cysteine on food intake and explored possible mechanisms by which it mediates this effect. L-cysteine dose dependently decreased food intake in both rats and mice following oral gavage and intraperitoneal administration. This reduction in food intake did not appear to be secondary to behavioural side effects or feelings of nausea. L-cysteine increased neuronal activation in the area postrema and nucleus tractus solitarius, delayed gastric emptying and suppressed plasma acyl-ghrelin levels. However, the anorectic effect of L-cysteine did not appear to depend on NMDA, GPRC6A or CCK-A receptors, nor on subdiaphragmatic vagal afferent signalling. Repeated administration of L-cysteine also decreased food intake in rats and diet-induced obese mice. The studies described in this thesis demonstrate the anorectic effects of L-cysteine and identify possible sites of action. It is likely that different amino acids exert different effects on appetite through a number of mechanisms, the combination of which contributes towards the success of high protein diets on body weight and appetite. This thesis provides a framework for future studies to investigate the therapeutic potential of combinations of amino acids that could provide a safe and practical therapeutic treatment for obesity.
Supervisor: Murphy, Kevin Sponsor: Biotechnology and Biological Sciences Research Council ; AstraZeneca (Firm)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral