This proposal describes a 3-year training program designed to provide the candidate (Dr. Scott E. Kanoski) with the expertise needed to incorporate a range of neuroanatomical, molecular, and other career oriented skills (e.g., mentoring, lab management, grant writing) that will broaden the scope of his obesity-focused research career. The proposed training plan will substantially benefit the candidate's ability to establish and maintain a productive independent behavioral neuroscience laboratory at the University of Southern California (USC) conducting research focused on obesity treatment and prevention. The candidate received a Ph.D. in Aug. 2009 and conducted research as a postdoctoral fellow in the Department of Psychology at the University of Pennsylvania. His position as Assistant Professor of Biology at USC begins January 2013. The Department of Biology at USC has a strong research tradition that will provide an ideal training and research environment for the candidate. The primary mentor, Dr. Alan Watts, Professor of Biology at USC, is a well-established researcher in the field of behavioral neuroscience and an expert in the neuroanatomical and neurochemical systems that control energy balance and metabolism. To facilitate the novel interdisciplinary approaches of the proposed research, the candidate will also be guided by co-mentor, Dr. David McKemy (USC), a prominent neurobiological researcher in the fields of somatosensation and nociception, and by Dr. Harvey Grill (University of Pennsylvania), a renowned expert in the neuroendocrine controls of feeding and energy expenditure. The research in this proposal will examine the novel hypothesis that the adipose cell-derived hormone leptin signals in the ventral hippocampus (VHPC), a brain region that regulates learning and motivational processes, to suppress motivational behaviors related to obtaining rewarding, palatable foods. The experiments described in the proposal use a rat model and integrate state-of-the-art neuroanatomical (immunohistochemistry and neurological tracers), molecular (immunoblot, qPCR), genetic (RNA interference), pharmacological (central delivery of agents), and behavioral techniques (learning and memory paradigms). Building directly on preliminary data presented in this proposal, experiments are designed to: 1) assess whether leptin receptor (LepRb) signaling in the VHPC is physiologically relevant to learned motivated behaviors directed towards food procurement, 2) identify the neural circuits that communicate in concert with the VHPC to reduce food intake via leptin signaling, and 3) identify whether food intake reduction by VHPC leptin involves brain-derived neurotrophic factor (BDNF) signaling. Results will contribute to the development of pharmacological obesity treatment by informing about the neuroendocrine and intracellular/molecular systems that control food intake and food-motivated behavior.

Public Health Relevance

Over 2/3 of adults in the USA are overweight or obese and there is currently a shortage of effective drug treatments for the excessive food intake that leads to obesity. Basic science is driving pharmaceutical developments for obesity by identifying specific brain chemical systems that reduce food intake. A novel approach is taken here;we believe that more progress can be made towards obesity treatment and reducing associated health care costs if basic research were to focus on understanding the mechanisms through which the hormone leptin signals in the hippocampus, a brain region that controls cognition and rewarding aspects of feeding, to reduce food intake and body weight.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
1K01DK097147-01A1
Application #
8581252
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Hyde, James F
Project Start
2013-08-01
Project End
2016-05-31
Budget Start
2013-08-01
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$94,728
Indirect Cost
$7,017
Name
University of Southern California
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Kanoski, S E; Ong, Z Y; Fortin, S M et al. (2015) Liraglutide, leptin and their combined effects on feeding: additive intake reduction through common intracellular signalling mechanisms. Diabetes Obes Metab 17:285-93
Hsu, Ted M; Hahn, Joel D; Konanur, Vaibhav R et al. (2015) Hippocampal GLP-1 receptors influence food intake, meal size, and effort-based responding for food through volume transmission. Neuropsychopharmacology 40:327-37
Hayes, Matthew R; Mietlicki-Baase, Elizabeth G; Kanoski, Scott E et al. (2014) Incretins and amylin: neuroendocrine communication between the gut, pancreas, and brain in control of food intake and blood glucose. Annu Rev Nutr 34:237-60
Kanoski, Scott E; Alhadeff, Amber L; Fortin, Samantha M et al. (2014) Leptin signaling in the medial nucleus tractus solitarius reduces food seeking and willingness to work for food. Neuropsychopharmacology 39:605-13
Ozek, Ceren; Kanoski, Scott E; Zhang, Zhong-Yin et al. (2014) Protein-tyrosine phosphatase 1B (PTP1B) is a novel regulator of central brain-derived neurotrophic factor and tropomyosin receptor kinase B (TrkB) signaling. J Biol Chem 289:31682-92