The physiological importance of central nervous system (CNS) regulation of metabolic fuels is well recognized, yet there is a resounding lack of systematic, coherent knowledge of the CNS control of metabolic fuels. This is both surprising and unfortunate: the CNS is the main regulator of energy stores and their replenishment, and the driving force behind changes in metabolic fuels during physiological or psychological stress. Disturbances of metabolic fuel regulation have definite pathologic consequences (e.g., retinopathy, nephropathy, hyperlipemia, atherosclerosis). The experiments proposed will use direct microinfusions of specific agonists and antagonists into the rat brain, and transections of brain pathways, to continue the systematic development of knowledge of the CNS control of blood glucose and free fatty acids, the two major metabolic fuels. These studies will determine the exact brain sites where beta-adrenergic, alpha-adrenergic, and histaminergic agonists affect metabolic fuel regulation, and which receptor types mediate these effects. Additional studies measuring blood insulin, glucagon, and catecholamines will determine the peripheral mechanisms which produce the changes seen in blood glucose and free fatty acids. Routine measurement of blood corticosterone, plus additional studies on gastric secretion, will show how specific these effects are for metabolic fuel regulation. Brain pathway transection studies will indicate the crucial pathways connecting regions mediating these effects. Agent interaction studies at specific sites will outline the pharmacological organization of processing at these sites. These studies will develop significant knowledge on the roles of central beta-adrenergic, alpha-adrenergic, and histaminergic systems in the CNS control of the metabolic fuels, glucose and free fatty acids. These studies will be crucial in designing future work measuring changes in specific neurotransmitter activities at specific sites during normal physiological events. The knowledge obtained will also be relevant to other fields, including the regulation of food intake and body weight and associated pathologies, CNS control of corticosterone secretion, control of adrenal catecholamine secretion, and neural control of the endocrine pancreas.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020660-07
Application #
3401185
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1985-09-30
Project End
1993-08-31
Budget Start
1991-09-01
Budget End
1993-08-31
Support Year
7
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Steinman, J L; Gunion, M W; Morley, J E (1994) Forebrain and hindbrain involvement of neuropeptide Y in ingestive behaviors of rats. Pharmacol Biochem Behav 47:207-14
Walford, R L; Harris, S B; Gunion, M W (1992) The calorically restricted low-fat nutrient-dense diet in Biosphere 2 significantly lowers blood glucose, total leukocyte count, cholesterol, and blood pressure in humans. Proc Natl Acad Sci U S A 89:11533-7
Babcock, A M; Barton, C; Gunion, M W et al. (1992) Bombesin-induced hypothermia and hypophagia are associated with plasma metabolic fuel alterations in the rat. Physiol Behav 51:933-8
Gunion, M W; Rosenthal, M J; Miller, S et al. (1992) Role of hypothalamic paraventricular nucleus alpha- and beta-adrenergic receptors in regulation of blood glucose, free fatty acids and corticosterone. Brain Res 588:84-96
Gunion, M W; Grijalva, C V; Tache, Y et al. (1991) Destruction of different fiber tracts underlies development of lateral hypothalamic lesion-induced hyperthermia and loss of bombesin-induced hypothermia. Brain Res 560:326-9
Gunion, M W; Rosenthal, M J; Morley, J E et al. (1991) mu-receptor mediates elevated glucose and corticosterone after third ventricle injection of opioid peptides. Am J Physiol 261:R70-81
Gunion, M W; Rosenthal, M J; Tatemoto, K et al. (1989) Intracranial microinfusion of pancreastatin elevates blood glucose, free fatty acids, and corticosterone in rats. Brain Res 485:251-7
Gunion, M W; Tache, Y; Rosenthal, M J et al. (1989) Bombesin microinfusion into the rat hypothalamic paraventricular nucleus increases blood glucose, free fatty acids and corticosterone. Brain Res 478:47-58
Gunion, M W; Rosenthal, M J; Tache, Y et al. (1988) Intrahypothalamic microinfusion of corticotropin-releasing factor elevates blood glucose and free fatty acids in rats. J Auton Nerv Syst 24:87-95
Gunion, M W; Tache, Y (1987) Intrahypothalamic microinfusion of corticotropin-releasing factor inhibits gastric acid secretion but increases secretion volume in rats. Brain Res 411:156-61

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