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Title: Metabolite and hormone rhythms : the effect of obesity type two diabetes and meal timing
Author: Isherwood, Cheryl M.
ISNI:       0000 0004 6061 5859
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 2017
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Daily rhythms are an important aspect of our physiology. A central clock in the hypothalamus tracks light-dark cycle and coordinates the ubiquitous peripheral clocks. This ensures that catabolic and anabolic biochemical pathways do not occur simultaneously. Disassociating the light-entrainable clocks in the suprachiasmatic nucleus (SCN) and food-entrainable peripheral clocks has metabolic consequences. Evidence from animal and human studies, point to short sleep duration, shift work, late night eating, obesity and type two diabetes (T2DM) all influencing, and being influenced by the circadian timing system. The studies within this thesis have set out to elucidate the effect of disturbed metabolism using models of obesity, T2DM and delaying a 3-meal a day feeding schedule by five hours. The effects of obesity and T2DM were examined by measuring circulating a large panel of amino acids, biogenic amines and glycerophospholipids using targeted LC/MS metabolomics, GI hormones, PAI-1, glucose, triglyceride. Approximately 1/2 of the GI hormones and 1/3 of the metabolites from each of the classes exhibited significant 24-h cosinor rhythms. Where rhythms were observed, neither obesity nor T2DM influenced the peak time or amplitude of the rhythm. The 5-h shift in meal timing did not affect the timing of the SCN-driven hormone melatonin. Approximately 1/3 of the metabolites exhibited significant cosine rhythms before and after the meal shift, half of which showed a 2-h phase delay after the late meal schedule. Some metabolites (citrulline, proline, AC-C2 and lysoPC a (C18:2, C20:3 and C20:4)) exhibited significant cosinor rhythms regardless of sleep, meal timing, age, BMI or insulin sensitivity. The results demonstrate that being obese or having T2DM affected the circulating concentrations, but did not affect the phase or amplitude of diurnal rhythms. Whereas a 5 h delay in meal timing led to a phase delay of metabolite rhythms, without affecting the amplitude.
Supervisor: Skene, D. J. Sponsor: Eurhythdia ; Diabetes UK ; Biotechnology and Biological Sciences Research Council ; Stockgrand Ltd
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available