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Title: Novel insights in imaging and function of human brown adipose tissue
Author: Reddy, Narendra Lakshmana
ISNI:       0000 0004 5366 0395
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2014
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Phenomenal rise in prevalence of obesity and its complications has made it imperative to tackle the issue on a war footing, especially given the failure of current life style and medical approaches. Clearly, alternate means of treating obesity need to be explored. In contrast to white adipose tissue (WAT), which stores excess energy, brown adipose tissue (BAT) dissipates chemical energy in the form of heat by uncoupling oxidative phosphorylation from electron transport chain, to maintain body temperature homeostasis. Recent revelation of functionality of BAT in adult humans provides an excellent opportunity of stimulating it to increase energy expenditure, in turn causing weight loss alongside improving lipid and glucose homeostasis. This thesis sought to investigate the physiological nature of brown fat, by exploring the environmental, biophysical and behavioural factors that can activate BAT. ¹⁸Fluoro-labelled-2-deoxyglucose Positron Emission Tomography (18F-FDG PET) is currently the gold standard and the most sensitive method to study BAT and its function. These studies concluded that younger-age, lower body mass index, female sex and cooler outdoor temperatures are strong determinant factors of BAT prevalence, activity and mass. Interestingly, modest elevation of thyroid hormones in a sustained iatrogenically created thyrotoxic state did not influence any of the BAT indices, contrary to conventional wisdom of strong stimulation, thus highlighting the complexity of BAT metabolism. Arguably, BAT has a role in diet-induced thermogenesis. Manipulation of diet-induced thermogenesis by prolonging meal duration to 40 minutes resulted in excess postprandial energy expenditure loss than shorter meal duration of 10 minutes. However, prolonged meal duration had weakly positive effect on metabolic biochemical markers and no influence on pancreatic and gut hormones relevant to appetite. These studies advocate life style and behavioural public health messages of lowering thermostat in living spaces and chewing the food adequately in order to obtain potential metabolic benefits. As a follow-up of exploring BAT's physiology, a successful attempt at characterising BAT's anatomy was made through novel imaging technique of Iterative Decomposition of Echo Asymmetry and Least Squares Estimation (IDEAL) Magnetic Resonance Imaging. The first ever non-PET imaging demonstration of adult human BAT using IDEAL MRI was achieved with immunohistochemical confirmation, and provided proof of concept for developing MR as a safe, non-radiation exposure imaging biomarker of BAT. In summary, this thesis provided useful insights into environmental, anthropometrical, behavioural, and hormonal factors regulating BAT, whilst also providing a proof of principle of an imaging tool to visualise full extent of both metabolically active and inactive BAT, aiding future pursuits of BAT therapeutics to combat the global obesity epidemic.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: R Medicine (General) ; RZ Other systems of medicine