Neuropeptide Y (NPY) is the most potent orexigenic, naturally-occurring signal known. Our previous studies showed that when feeding is desired NPY is released at a high rate into the paraventricular nucleus (PVN) of the hypothalamus and as rats consumed food, NPY hypersecretion ceased. Based on our recent findings, we now propose to test the hypothesis that an interconnected orexigenic network exists in the rat hypothalamus and that the NPY system exerts a regulatory influence in this circuitry.
Aim i is to identify the cellular and molecular events in the dynamics of NPY secretion (synthesis, storage and release) in association with food intake. After obtaining this basic information, Aim 2 will evaluate how the interconnected orexigenic network operates.
Aim 3 is to validate the hypothesis that the cessation of NPY hypersecretion in the PVN that occurs in association with food consumption is due to the inhibitory action of locally-produced peptides. The release, synthesis and postsynaptic effects of the peptidergic components of the newly identified orexigenic network will be assessed in vivo and in vitro. The sequential studies in this proposal are designed to first identify the important signals that stimulate or inhibit feeding and then to understand the mechanism of their action and of the factors that regulate their release and synthesis. Information gained from these studies should unravel the operation, physiological roles and relationships of three peptide signals that comprise the newly identified excitatory orexigenic network and form the basis for future studies to elucidate the etiology of certain eating disorders and obesity of hypothalamic origin.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK037273-08A3
Application #
2140052
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1986-06-01
Project End
1999-05-31
Budget Start
1995-06-01
Budget End
1996-05-31
Support Year
8
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Florida
Department
Neurosciences
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Turner, Russell T; Kalra, Satya P; Wong, Carmen P et al. (2013) Peripheral leptin regulates bone formation. J Bone Miner Res 28:22-34
Iwaniec, Urszula T; Boghossian, St├ęphane; Trevisiol, Cynthia H et al. (2011) Hypothalamic leptin gene therapy prevents weight gain without long-term detrimental effects on bone in growing and skeletally mature female rats. J Bone Miner Res 26:1506-16
Kalra, S P (2011) Pivotal role of leptin-hypothalamus signaling in the etiology of diabetes uncovered by gene therapy: a new therapeutic intervention? Gene Ther 18:319-25
Jackson, M A; Iwaniec, U T; Turner, R T et al. (2011) Effects of increased hypothalamic leptin gene expression on ovariectomy-induced bone loss in rats. Peptides 32:1575-80
Kalra, Satya P; Kalra, Pushpa S (2010) Neuroendocrine control of energy homeostasis: update on new insights. Prog Brain Res 181:17-33
Kalra, Satya P; Dube, Michael G; Iwaniec, Urszula T (2009) Leptin increases osteoblast-specific osteocalcin release through a hypothalamic relay. Peptides 30:967-73
Kojima, Shinya; Asakawa, Akihiro; Amitani, Haruka et al. (2009) Central leptin gene therapy, a substitute for insulin therapy to ameliorate hyperglycemia and hyperphagia, and promote survival in insulin-deficient diabetic mice. Peptides 30:962-6
Kalra, Satya P (2009) Central leptin gene therapy ameliorates diabetes type 1 and 2 through two independent hypothalamic relays; a benefit beyond weight and appetite regulation. Peptides 30:1957-63
Iwaniec, U T; Dube, M G; Boghossian, S et al. (2009) Body mass influences cortical bone mass independent of leptin signaling. Bone 44:404-12
Kalra, Satya P (2008) Central leptin insufficiency syndrome: an interactive etiology for obesity, metabolic and neural diseases and for designing new therapeutic interventions. Peptides 29:127-38

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