This application for support of work examining the mediation of two distinct metabolic controls on food intake, glucoprivic and lipoprivic controls. Prior work by the investigator has demonstrated different sites for activation of glucoprivic and lipoprivic feeding: glucoprivic controls appear to be located in the hindbrain and lipoprivic controls depend upon receptors associated with abdominal vagal sensory neurons. The proposal has three specific aims.
The first aim i s to precisely localize hindbrain glucoreceptor neurons that mediate glucoprivic feeding. Experiments addressing this aim map hindbrain sites at which feeding behavior can be elicited by nanoliter injections of glucoprivic agents. Experiments also asses the effects of lesions of apparent glucoreceptive cell groups on the ability of 5TG to elicit of food intake and fos expression.
The second aim i s to identify the specific neuronal pathways responsible for transmission of sensory information crucial for elicitation of both glucoprivic and lipoprivic feeding from hindbrain to forebrain sites. Experiments addressing this aim will utilize c-fos immunohistochemistry to identify retrogradely labeled neurons that are activated by glucoprivation or lipoprivation and by examining the feeding response and fos expression to glucoprivic and lipoprivic agents in rats in which aspects of these neural pathways have been lesioned. In addition, under this aim, nutrients that block lipoprivic feeding will be systemically infused to examine their effect on fos expression at various levels of the identified neural system mediating lipoprivic feeding.
The third aim of the project is to identify the neurotransmitter phenotype of the neurons mediating glucoprivic and lipoprivic feeding. Hindbrain catecholamine cell groups will be examined for expression of fos in response to glucoprivation. In addition, glucoprivic feeding and induction of fos in the brain will be studied following lateral ventricular injections of 6-hydroxydopamine to determine the necessity of catecholamine mediation. Finally, a potential role for the neuropeptide galanin in lipoprivic feeding will be examined. The investigator has previously demonstrated that a galanin receptor antagonist microinjected into the fourth ventricle reduced lipoprivic feeding. This result will be extended by studying effects of microinjections of galanin and a galanin antagonist in specific brain sites important for lipoprivic feeding. Thus, the overall goals of this project are to 1) identify neuronal populations involved in glucoprivic and lipoprivic feeding, 2) identify the local neurotransmitters on which these responses depend and 3) identify how the actions of these neuronal populations are modified under different metabolic states.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK040498-08
Application #
2391414
Study Section
Biopsychology Study Section (BPO)
Project Start
1989-04-01
Project End
2000-03-31
Budget Start
1997-04-01
Budget End
1998-03-31
Support Year
8
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Washington State University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
041485301
City
Pullman
State
WA
Country
United States
Zip Code
99164
Li, Ai-Jun; Wang, Qing; Dinh, Thu T et al. (2016) Mercaptoacetate blocks fatty acid-induced GLP-1 secretion in male rats by directly antagonizing GPR40 fatty acid receptors. Am J Physiol Regul Integr Comp Physiol 310:R724-32
Li, Ai-Jun; Wang, Qing; Davis, Hana et al. (2015) Orexin-A enhances feeding in male rats by activating hindbrain catecholamine neurons. Am J Physiol Regul Integr Comp Physiol 309:R358-67
Li, Ai-Jun; Wang, Qing; Elsarelli, Megan M et al. (2015) Hindbrain Catecholamine Neurons Activate Orexin Neurons During Systemic Glucoprivation in Male Rats. Endocrinology 156:2807-20
Li, Ai-Jun; Wang, Qing; Dinh, Thu T et al. (2014) Stimulation of feeding by three different glucose-sensing mechanisms requires hindbrain catecholamine neurons. Am J Physiol Regul Integr Comp Physiol 306:R257-64
Darling, Rebecca A; Zhao, Huan; Kinch, Dallas et al. (2014) Mercaptoacetate and fatty acids exert direct and antagonistic effects on nodose neurons via GPR40 fatty acid receptors. Am J Physiol Regul Integr Comp Physiol 307:R35-43
Wiater, Michael F; Li, Ai-Jun; Dinh, Thu T et al. (2013) Leptin-sensitive neurons in the arcuate nucleus integrate activity and temperature circadian rhythms and anticipatory responses to food restriction. Am J Physiol Regul Integr Comp Physiol 305:R949-60
Li, Ai-Jun; Wang, Qing; Dinh, Thu T et al. (2013) Hindbrain catecholamine neurons control rapid switching of metabolic substrate use during glucoprivation in male rats. Endocrinology 154:4570-9
Routh, Vanessa H; Donovan, Casey M; Ritter, Sue (2012) 2. Hypoglycemia Detection. Transl Endocrinol Metab 3:47-87
Li, Ai-Jun; Wiater, Michael F; Oostrom, Marjolein T et al. (2012) Leptin-sensitive neurons in the arcuate nuclei contribute to endogenous feeding rhythms. Am J Physiol Regul Integr Comp Physiol 302:R1313-26
Wiater, M F; Mukherjee, S; Li, A-J et al. (2011) Circadian integration of sleep-wake and feeding requires NPY receptor-expressing neurons in the mediobasal hypothalamus. Am J Physiol Regul Integr Comp Physiol 301:R1569-83

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