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- W2531403325 abstract "Cocaine- and amphetamine- regulated transcript (CART) was originally identified as amRNA transcript upregulated in rats in response to administration of cocaine andamphetamine. CART is widely expressed in the central nervous system (CNS) with highlevels of expression in hypothalamic nuclei such as the arcuate nucleus (ARC).CART was initially thought to act as an anorectic peptide since it is coexpressed with theanorectic neuropeptide pro-opiomelanocortin (POMC) in the ARC. In addition,intracerebroventricular (ICV) administration of CART (55-102) peptide inhibits feeding andadministration of anti-CART antibody results in stimulation of feeding. However, subsequentstudies have suggested CART may also act as an orexigen since injection of CART (55-102)specifically into the ARC and ventromedial nucleus (VMN) of the hypothalamus results in asignificant increase in food intake. These data suggest CART acts through both anorectic andorexigenic circuits. Given the importance of the hypothalamus in the regulation of energyhomeostasis, and the role of the ARC in integrating peripheral signals, it is essential toelucidate the role of ARC derived CART. In order to elucidate CART’s true physiologicalrole in the ARC I used a combination of genetic approaches. I generated a recombinantAdeno-associated virus (rAAV) expressing CART antisense (CART-AS) and a transgenicmouse model which utilises the POMC promoter to drive expression of CART-AS.In the transgenic CART-AS model mice exhibited a significantly higher body weight relativeto control animals, no significant difference in food intake was observed. In addition, miceexpressing the CART-AS transgene demonstrated a reduction in uncoupling protein-1 (UCP-1) mRNA expression in brown adipose tissue (BAT) which is suggestive of decreasedthermogenesis. This may explain the observed increase in body weight in the transgenicmice. Bilateral intra-ARC injections of rAAV-CART-AS resulted in a significant increase incumulative food intake and body weight gain compared to control animals. There was nosignificant difference in activity or metabolism levels.The data presented in my thesis provides an important contribution to understanding the roleof CART within the ARC. The results from my genetic studies appear to suggest that ARCderived CART has an anorectic role." @default.
- W2531403325 created "2016-10-21" @default.
- W2531403325 creator A5085406457 @default.
- W2531403325 date "2010-09-21" @default.
- W2531403325 modified "2023-09-28" @default.
- W2531403325 title "To investigate the physiological role of arcuate nucleus cocaine- and amphetamine- regulated transcript in energy homeostasis" @default.
- W2531403325 doi "https://doi.org/10.25560/5933" @default.
- W2531403325 hasPublicationYear "2010" @default.
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