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Title: The effects of dietary interventions on metabolic flexibility
Author: Lim, Chong
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2017
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Metabolic flexibility is defined as the ability of an organism to adapt from fuel oxidation to fuel availability. It is well established that obesity results in loss of metabolic flexibility, however, the exact mechanism remains unclear. Therefore, it is critical to understand the mechanism underlying metabolic flexibility to tackle the epidemic of obesity. An energy-restricted diet will lead to weight loss. However, little is known regarding the mechanisms behind the improvement in metabolic flexibility with weight loss following an energy-restricted diet. In investigation 1, I compared the effects of an energy-restricted diet and a control diet over 12 weeks on overweight and obese volunteers to elucidate the underlying mechanism of metabolic flexibility. The results demonstrated that weight loss is associated with significant reductions in body fat composition, waist circumference, hip circumference, visceral fats, blood pressure, and an improvement in postprandial insulin sensitivity. This translates into an improvement in metabolic health and metabolic flexibility. However, the underlying mechanism remained unclear. Furthermore, dietary modification using short chain fatty acids provides an attractive avenue to improve metabolic flexibility. However, the evidence for the role of short chain fatty acids in improving human metabolic flexibility is lacking. In order to investigate the effects of short chain fatty acids on metabolic flexibility, I used encapsulated sodium propionate, which is a novel method to explore its effects on glucose homeostasis. Investigation 2 consists of two parts. The first part of the study was to demonstrate the pharmacokinetic profile of encapsulated sodium propionate. The results demonstrated no significant changes in serum propionate concentrations following ingestion of encapsulated sodium propionate. The second part of the study was designed to establish the most effective dose of sodium propionate in improving glucose homeostasis. Results from this part of the study demonstrated no significant change in beta cell function.
Supervisor: Frost, Gary Sponsor: Imperial College London
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral