Abstract

The specific aims remain essentially the same for this long-running project; i.e., to elucidate how adiposity signals interact with the brain to influence food intake and body weight. The adiposity signals now include leptin as well as insulin.
Specific Aim 1 will determine the interactions of insulin with the hypothalamic propiomelanocoritin (POMC) and neuropeptide Y (NPY) systems. The hypothesis driving the experiments is that insulin will potentiate the POMC system and inhibit the NPY system.
Specific Aim 2 will determine the interactions of insulin and leptin within the brain. The hypothesis is that the two peptides will synergistically elicit a net catabolic action.
Specific Aim 3 will assess the hypothesis that a major gender difference exists in the central control of energy homeostasis, with insulin controlling the male system and leptin controlling the female system. Finally, Specific Aim 4 will determine the effect of eliminating insulin signaling in the brain by creating mice with brain-specific insulin receptor deletions. All of the experiments are directly relevant to emerging therapeutic approaches to the treatment of obesity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK017844-28
Application #
6634844
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Yanovski, Susan Z
Project Start
1978-07-01
Project End
2006-05-31
Budget Start
2003-07-01
Budget End
2004-05-31
Support Year
28
Fiscal Year
2003
Total Cost
$335,791
Indirect Cost

  Institution

Name
University of Cincinnati
Department
Psychiatry
Type
Schools of Medicine
DUNS #
041064767
City
Cincinnati
State
OH
Country
United States
Zip Code
45221

  Publications

Woods, Stephen C; May-Zhang, Aaron A; Begg, Denovan P (2018) How and why do gastrointestinal peptides influence food intake? Physiol Behav 193:218-222
Shen, Ling; Wang, David Q H; Xu, Meifeng et al. (2017) BDNF/TrkB signaling mediates the anorectic action of estradiol in the nucleus tractus solitarius. Oncotarget 8:84028-84038
Fischer, Katrin; Ruiz, Henry H; Jhun, Kevin et al. (2017) Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis. Nat Med 23:623-630
May, Aaron A; Liu, Min; Woods, Stephen C et al. (2016) CCK increases the transport of insulin into the brain. Physiol Behav 165:392-7
May, Aaron A; Bedel, Nicholas D; Shen, Ling et al. (2016) Estrogen and insulin transport through the blood-brain barrier. Physiol Behav 163:312-321
Begg, Denovan P; May, Aaron A; Mul, Joram D et al. (2015) Insulin Detemir Is Transported From Blood to Cerebrospinal Fluid and Has Prolonged Central Anorectic Action Relative to NPH Insulin. Diabetes 64:2457-66
Wang, Fei; Yang, Qing; Huesman, Sarah et al. (2015) The role of apolipoprotein A-IV in regulating glucagon-like peptide-1 secretion. Am J Physiol Gastrointest Liver Physiol 309:G680-7
Mc Allister, Eugenia; Pacheco-Lopez, Gustavo; Woods, Stephen C et al. (2015) Inconsistencies in the hypophagic action of intracerebroventricular insulin in mice. Physiol Behav 151:623-8
Grillo, Claudia A; Piroli, Gerardo G; Lawrence, Robert C et al. (2015) Hippocampal Insulin Resistance Impairs Spatial Learning and Synaptic Plasticity. Diabetes 64:3927-36
Chambers, Adam P; Smith, Eric P; Begg, Denovan P et al. (2014) Regulation of gastric emptying rate and its role in nutrient-induced GLP-1 secretion in rats after vertical sleeve gastrectomy. Am J Physiol Endocrinol Metab 306:E424-32

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