Feeding regulation is essential to ensure that animals consume calories in proportion to their energy requirements. An imbalance of neuromodulatory systems that regulate feeding may result in obesity and eating disorders, with significant health-related consequences. The long-term objective of this proposal is to increase understanding of the molecular signaling pathways that regulate food intake and how they interact, crucial for devising rational approaches toward controlling obesity and eating disorders. The monoaminergeric neurotransmitters, dopamine and serotonin, oppositely regulate feeding. In mammals, dopamine promotes feeding and serotonin inhibits it. Preliminary studies of this proposal showed that dopamine and serotonin regulate feeding in the fruit fly Drosophila melanogaster and identified the dopaminergic neurons that promote feeding and serotonergic neurons that inhibit feeding. The relative simplicity of the fruit fly nervous system provides a tractable model to dissect how dopamine and serotonin oppositely regulate feeding.
Aim 1 will examine whether the activity of serotonergic neurons bidirectionally controls feeding behavior in response to external gustatory cues and internal physiological state.
Aim 2 will test the hypothesis that dopamine and serotonin act over short timescales to regulate feeding during a meal as well as over longer timescales to adjust feeding based on internal physiological state.
Aim 3 will examine whether dopamine and serotonin are opponent signals that act on the same or different neurons to modulate feeding. The proposed molecular genetic, electrophysiological and behavioral approaches will provide a comprehensive analysis of dopamine and serotonin function that is difficult to achieve in other systems. These studies will provide insight into how the monoaminergic neurotransmitter systems exercise control over feeding and will significantly advance understanding of feeding modulation, an essential foundation relevant for human health and disease.

Public Health Relevance

This research examines the molecular signaling pathways that regulate feeding and how they interact. This basic research is a crucial step in understanding how feeding is regulated and how misregulation leads to obesity and eating disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK098747-01
Application #
8482582
Study Section
Molecular Neurogenetics Study Section (MNG)
Program Officer
Karp, Robert W
Project Start
2013-04-25
Project End
2018-03-31
Budget Start
2013-04-25
Budget End
2014-03-31
Support Year
1
Fiscal Year
2013
Total Cost
$324,987
Indirect Cost
$107,487
Name
University of California Berkeley
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Youn, Hyesoo; Kirkhart, Colleen; Chia, Justine et al. (2018) A subset of octopaminergic neurons that promotes feeding initiation in Drosophila melanogaster. PLoS One 13:e0198362
Cheung, Samantha K; Scott, Kristin (2017) GABAA receptor-expressing neurons promote consumption in Drosophila melanogaster. PLoS One 12:e0175177
Jourjine, Nicholas; Mullaney, Brendan C; Mann, Kevin et al. (2016) Coupled Sensing of Hunger and Thirst Signals Balances Sugar and Water Consumption. Cell 166:855-866
Gray, Joshua P; Burgos, Delaine Zayasbazan; Yuan, Tao et al. (2016) Thymoquinone, a bioactive component of Nigella sativa, normalizes insulin secretion from pancreatic ?-cells under glucose overload via regulation of malonyl-CoA. Am J Physiol Endocrinol Metab 310:E394-404
Gray, Joshua P; Karandrea, Shpetim; Burgos, Delaine Zayasbazan et al. (2016) NAD(P)H-dependent quinone oxidoreductase 1 (NQO1) and cytochrome P450 oxidoreductase (CYP450OR) differentially regulate menadione-mediated alterations in redox status, survival and metabolism in pancreatic ?-cells. Toxicol Lett 262:1-11
Pool, Allan-Hermann; Scott, Kristin (2014) Feeding regulation in Drosophila. Curr Opin Neurobiol 29:57-63
Pool, Allan-Hermann; Kvello, Pal; Mann, Kevin et al. (2014) Four GABAergic interneurons impose feeding restraint in Drosophila. Neuron 83:164-77