The overall goal of the research is to elucidate the role played by several eptidergic hormones in the normal regulation of food intake and body weight in rats. The driving hypothesis is that body weight (or, more specifically, body adiposity) is precisely regulated, and that this regulation depends at least in part upon adiposity-related signals that travel in the blood. There is considerable evidence that the pancreatic hormone insulin is one such signal since its secretion is directly proportional to adiposity and since it gains access to the brain via a receptor-mediated transport system. We have already found that adding insulin in small quantities to the brain causes animals to eat less and lose weight. We are now concentrating upon how insulin, once it enters the brain, interacts with other systems important in the control of food intake. In particular, we will investigate the interaction of central insulin with anorexigenic peptides (cholecystokinin, for example), with orexigenic peptides (e.g., NPY), and with compounds including adrenal steroids which alter the brain's sensitivity to insulin. We will also investigate the brain-insulin system and the intake, of specific dietary macronutrients (fats, carbohydrates and proteins). Finally, we will determine how central insulin influences energy expenditure and body metabolism. These experiments are critical for a complete understanding of the normal controls over weight regulation and may suggest novel therapeutic strategies for eating disorders and/or obesity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
2R37DK017844-18
Application #
3483225
Study Section
Biopsychology Study Section (BPO)
Project Start
1978-07-01
Project End
1998-06-30
Budget Start
1993-08-01
Budget End
1994-06-30
Support Year
18
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Arts and Sciences
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
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
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
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
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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