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Title: Peripheral regulation of energy balance in the laboratory mouse
Author: Haggerty, Carolyn
ISNI:       0000 0001 3523 9300
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2006
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Obesity is a complex disease that is affected by varoiius contributing factors, including resting metabolic rate (RMR), which is genetically determined.  High RMR  has been implicated as protective against the development of obesity, hence genes linked to RMR are potential therapeutic targets in the treatment of obesity. Gene expression profiles of brown adipose tissue (BAT), liver and skeletal muscle were generated to compare mice grouped for high and low RMR.  BAT had the highest number of differential expressed genes, which were clustered and displayed two distinct clusters, corresponding to mice with either high or low RMR.  The genes up-regulated in BAT of the high RMR mice provided two possible mechanisms contributing to the elevated resting metabolism.  First was the potential increase in fatty acid oxidation.  The up-regulation of AMP-activated protein kinase (AMPK) may have inhibited acetyl-CoA carboxylase (ACC2) via increased phosphorylation, which was verified by western blotting.  The inhibition of ACC2 activated fatty acid oxidation, as carnitine palmitoly transferase-1 (CPT1) was released from its inhibition by malonyl-CoA, thus allowing the entry of fatty acids to the mitochondria for fatty acid oxidation.  The second mechanism was associated with the calcium-regulatory proteins, which may be involved in the transport of calcium in and out of the endoplasmic reticulum (ER).  Decreased intracellular calcium levels, potentially through calcium-leak channels, may have elevated ATP hydrolysis of the sarco/endoplasmic Ca2+ ATPase (SERCA) for calcium reuptake, to maintain intracellular calcium levels at the ER.  Thus, increased ATP hydrolysis by SERCA and calcium regulatory genes, may be an additional or alternative process to UCP1-mediated thermogenesis in BAT which will boost RMR.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available