Abstract/Details

Novel roles for TRPA1 and TRPV1 in nutrient sensing and obesity


2011 2011

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Abstract (summary)

In the first part of this thesis I explored a role for the capsaicin receptor TRPV1 in the regulation of feeding and body mass. On a diet containing 4.5% fat, wild-type and TRPV1-null mice gained equivalent body mass. On a diet containing 11% fat, however, TRPV1-null mice gained significantly less mass and adiposity; at 44 weeks the mean body weights of wild-type and TRPV1-null mice were 51 and 34 g respectively. Both groups of mice consumed equivalent energy and absorbed similar amounts of lipids. TRPV1-null mice, however, exhibited a significantly greater thermogenic capacity. In contrast to earlier reports, I found that TRPV1-null animals have higher blood glucose levels. Further, I demonstrate that 3T3-L1 preadipocytes expressed functional calcitonin gene-related peptide (CGRP) receptors suggesting a potential neurogenic mechanism by which TRPV1-expressing sensory neurons may regulate adiposity. Taken together, these data support a role for TRPV1 expressing sensory nerves in regulating energy and fat metabolism.

In the second part of this thesis I investigated the role of TRPA1, a nociceptive ion channel, as a fatty acid receptor and modulator of gastric function. Polyunsaturated fatty acids are known agonists for a variety of receptors including members of the transient receptor potential ion channel family. Long chain polyunsaturated fatty acids such as DHA and EPA, predominately found in oily fish, are recognized by their aversive, pungent quality. These properties make DHA a prime candidate to activate TRPA1 within the intestinal mucosa. Indeed, I found that DHA directly activates TRPA1 without covalently binding to the channel. Further, activation of TRPA1 on intestinal-derived cell lines induces secretion of CCK. Taken together these studies suggest DHA can modulate digestive mechanisms through TRPA1.

Indexing (details)


Subject
Neurosciences;
Pharmacology;
Physiology
Classification
0317: Neurosciences
0419: Pharmacology
0719: Physiology
Identifier / keyword
Health and environmental sciences; Biological sciences; Body mass; Capsaicin receptors; Feeding; Nutrients; Obesity; TRPA1
Title
Novel roles for TRPA1 and TRPV1 in nutrient sensing and obesity
Author
Motter, Arianne Louise
Number of pages
122
Publication year
2011
Degree date
2011
School code
0076
Source
DAI-B 72/11, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9781124826004
Advisor
Ahern, Gerard P.
Committee member
Partridge, John; Wolfe, Barry; Xu, Bajoi; Zukowska, Zofia
University/institution
Georgetown University
Department
Pharmacology
University location
United States -- District of Columbia
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3468533
ProQuest document ID
888057981
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/888057981/abstract
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