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Subcellular distribution of lipid metabolising enzymes in human skeletal muscle

Clark, Juliette A. (2012)
Ph.D. thesis, University of Birmingham.

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In obesity, lipids stored in muscle as lipid droplets (LDs) lead to accumulation of fatty acid (FA) metabolites and insulin resistance. This research involves development of immunofluorescence microscopy methods to generate novel information on the subcellular content and distribution of key enzymes that play a role in the underlying mechanisms. Chapters 3 and 4 describe visualisation of two lipid synthesising enzymes. Both are more abundant in type I muscle fibres. Chapter 5 reveals no differences between these enzymes in non obese and obese elderly women. Chapter 6 reveals that a key lipolytic enzyme (ATGL) has a higher content in type I fibres, but its activator does not. Chapter 7 describes visualisation of SNAP23 and reveals a high content at the plasma membrane and mitochondria and low content in LDs. Chapter 8 fails to observe a difference between obese and non obese elderly women in plasma membrane SNAP23, and therefore fails to confirm the hypothesis that LDs hijack SNAP23. However, obese women have less SNAP23 in mitochondria and this may limit FA oxidation. In conclusion this thesis describes several novel mechanisms by which obesity leads to accumulation of FA metabolites and insulin resistance. The developed methods will be a valuable novel tool for future diabetes research.

Type of Work:Ph.D. thesis.
Supervisor(s):Wagenmakers, Anton and Shaw, Chris
School/Faculty:Colleges (2008 onwards) > College of Life & Environmental Sciences
Department:School of Sport and Exercise Science
Subjects:QH301 Biology
QM Human anatomy
QP Physiology
RA0421 Public health. Hygiene. Preventive Medicine
RC Internal medicine
Institution:University of Birmingham
ID Code:3378
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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