Recent molecular and genetic studies indicate that a neuropeptide Y (NPY) mediated signaling pathway, which is conserved among animals including worms and humans, is involved in regulating feeding behavior. However, the mechanism for its regulation is not understood. The long term goal of this proposal is to understand the role of Drosophila neuropeptide F(NPF), a human NPY homolog, in modulating feeding behavior, the underlying mechanism(s), and its functional relationship to vertebrate neuropeptide Y family molecules. Drosophila is the only invertebrate model organism where homologs of NPY and its receptors have been identified. Using whole mount in situ RNA hybridization and immunocytochemistry, we showed that dNPF is expressed in both CNS and gut In larval CNS, dNPFergic neurons of the brain innervate subesophageal, thoracic, and abdominal ganglia, and may thereby act as neurotransmitters for mediating brain control of feeding behavior. We also found that gustatory stimulation by sugars induces dNPF expression in two additional neurons of larval subesophageal ganglion. The expression remains strong long after sugar withdrawl, implicating dNPF in mediating carbohydrate conditioning of fly CNS. The dNPF midgut expression is enhanced by food uptake, and reduced by starvation. One of the putative dNPF receptors is expressed in larval gut, brain and possibly salivary glands. Thus, dNPF may also function as a gut hormone that coordinates feeding associated activities in diverse tissues. In this application, we propose to directly test the specific roles of dNPF in transgenic flies by addressing the following specific aims: 1) Constructing gain-of-function transgenic Drosophila larvae through controlled ectopic dNPF expression and analyzing their feeding behaviors; 2) Cloning and characterization of cis regulatory elements of dNPF using UAStauGFP reporter system; 3) constructing loss-of-function transgenic larvae through targeted functional knockout of dNPF and determining the specific roles of brain, subesophageal ganglion and midgut dNPF in feeding behavior. These studies should provide general insights into the signaling mechanism for feeding regulation in invertebrates as well as higher animals including humans.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK058348-02
Application #
6517821
Study Section
Special Emphasis Panel (ZRG1-IFCN-2 (01))
Program Officer
Yanovski, Susan Z
Project Start
2001-05-01
Project End
2004-04-30
Budget Start
2002-05-01
Budget End
2003-04-30
Support Year
2
Fiscal Year
2002
Total Cost
$240,730
Indirect Cost
Name
University of Georgia
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Athens
State
GA
Country
United States
Zip Code
30602
Branch, Audrey; Zhang, Yiwen; Shen, Ping (2017) Genetic and Neurobiological Analyses of the Noradrenergic-like System in Vulnerability to Sugar Overconsumption Using a Drosophila Model. Sci Rep 7:17642
Branch, Audrey; Bobilev, Anastasia; Negrao, Nuria Waddington et al. (2015) Prevention of palatable diet-induced hyperphagia in rats by central injection of a VEGFR kinase inhibitor. Behav Brain Res 278:506-13
Wang, Yonghua; Pu, Yuhan; Shen, Ping (2013) Neuropeptide-gated perception of appetitive olfactory inputs in Drosophila larvae. Cell Rep 3:820-30
Zhang, Ting; Branch, Audrey; Shen, Ping (2013) Octopamine-mediated circuit mechanism underlying controlled appetite for palatable food in Drosophila. Proc Natl Acad Sci U S A 110:15431-6
Xu, Jie; Li, Mo; Shen, Ping (2010) A G-protein-coupled neuropeptide Y-like receptor suppresses behavioral and sensory response to multiple stressful stimuli in Drosophila. J Neurosci 30:2504-12
Xu, Jie; Sornborger, Andrew T; Lee, Jennifer K et al. (2008) Drosophila TRPA channel modulates sugar-stimulated neural excitation, avoidance and social response. Nat Neurosci 11:676-82
Lingo, P R; Zhao, Z; Shen, P (2007) Co-regulation of cold-resistant food acquisition by insulin- and neuropeptide Y-like systems in Drosophila melanogaster. Neuroscience 148:371-4
Wu, Qi; Zhao, Zhangwu; Shen, Ping (2005) Regulation of aversion to noxious food by Drosophila neuropeptide Y- and insulin-like systems. Nat Neurosci 8:1350-5
Wen, Tieqiao; Parrish, Clayton A; Xu, Dan et al. (2005) Drosophila neuropeptide F and its receptor, NPFR1, define a signaling pathway that acutely modulates alcohol sensitivity. Proc Natl Acad Sci U S A 102:2141-6
Wu, Qi; Zhang, Yan; Xu, Jie et al. (2005) Regulation of hunger-driven behaviors by neural ribosomal S6 kinase in Drosophila. Proc Natl Acad Sci U S A 102:13289-94

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