The goal of this proposal is to identify the ligand(s) and to characterize RGS/G-protein coupled pathway(s) controlling RGS expression, GAP activity, and down stream responses in liver of fasted and fed mice. We found that RGS/G protein signaling regulates transitions from the fasted to fed state. G protein coupled receptors in the central nervous system and periphery convey many of the important signals that regulate feeding behavior. We will investigate how fatty acids, hormones, and/or neuroendocrine factors regulate the expression of Regulators of G protein Signaling (RGS) proteins, and their G protein substrates, in fasted and fed mice. Our work showed that RGS proteins are critical regulators of Gi- and Gq-signaling, both to assemble signaling complexes and to provide feedback regulation of signaling pathways. RGS proteins are GTPase activating proteins (GAPs) that inhibit G protein signaling. Our hypothesis is that RGS GAP activity is regulated by preprandial and satiety signals to control G protein signaling pathways in liver. We found that RGS mRNA is up-regulated by fasting and down-regulated by feeding in a leptin-dependent manner. Our hypothesis is that this RGS gene is a feedback regulator of G protein signaling pathway(s) that controls fatty acid oxidation. To test this hypothesis we propose the following Specific Aims.
Aim 1 : Determine if RGS transgenic expression regulates feeding, fatty acid and/or glucose metabolism.
Aim 2 : Determine if RGS deficiency alters feeding or disrupts fatty acid and glucose metabolism.
Aim 3 : Identify the preprandial agonist(s) that induce RGS expression. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM061395-09A3S1
Application #
7288062
Study Section
Gastrointestinal Cell and Molecular Biology Study Section (GCMB)
Program Officer
Dunsmore, Sarah
Project Start
2000-04-01
Project End
2010-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
9
Fiscal Year
2006
Total Cost
$45,993
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Pharmacology
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
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