This is a renewal for 5 additional years a grant on the hepatic influences upon feeding. The PI and his colleagues have completed extensive work with the fructose analogue, 2,5-AM. The drug reduces ATP formation in the liver and a signal is relayed to the brain that causes initiation of eating. The PI now proposes to complete the extensive studies necessary to demonstrate that a drug does or does not act in the liver to influence eating with three other antimetabolites: Ouabain, ethionine and mercaptoacetate. In related experiments, labelled drug will be given and the liver, brain, kidneys, epididymal fat and muscle analyzed for uptake. In a second series of proposed experiments, intraportal and intrahepatic infusions of 2,5-AM will be compared with the hepatic branch of the vagus intact or cut. The purpose is to determine if 2,5-AM-elicited eating is caused by hepatic signals travelling in several branches of the vagus or else in several organs in the hepatic bed. A third series of experiments will use two methods, cFOS induction and local cerebral glucose utilization of labelled 2-deoxyglucose, to ascertain which areas of the lower brainstem are activated by 2,5-AM.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK036339-09A2
Application #
2139775
Study Section
Special Emphasis Panel (ZRG1-BPO (02))
Project Start
1986-01-01
Project End
1999-03-31
Budget Start
1995-04-01
Budget End
1996-03-31
Support Year
9
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Monell Chemical Senses Center
Department
Type
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Horn, Charles C; Friedman, Mark I (2005) Thoracic cross-over pathways of the rat vagal trunks. Brain Res 1060:153-61
Horn, Charles C; Richardson, Eric J; Andrews, Paul L R et al. (2004) Differential effects on gastrointestinal and hepatic vagal afferent fibers in the rat by the anti-cancer agent cisplatin. Auton Neurosci 115:74-81
Horn, Charles C; Ji, Hong; Friedman, Mark I (2004) Etomoxir, a fatty acid oxidation inhibitor, increases food intake and reduces hepatic energy status in rats. Physiol Behav 81:157-62
Horn, Charles C; Friedman, Mark I (2004) Separation of hepatic and gastrointestinal signals from the common ""hepatic"" branch of the vagus. Am J Physiol Regul Integr Comp Physiol 287:R120-6
Horn, Charles C; Friedman, Mark I (2003) Detection of single unit activity from the rat vagus using cluster analysis of principal components. J Neurosci Methods 122:141-7
Horn, C C; Tordoff, M G; Friedman, M I (2001) Role of vagal afferent innervation in feeding and brain Fos expression produced by metabolic inhibitors. Brain Res 919:198-206
Bachmanov, A A; Reed, D R; Tordoff, M G et al. (2001) Nutrient preference and diet-induced adiposity in C57BL/6ByJ and 129P3/J mice. Physiol Behav 72:603-13
Friedman, M I; Harris, R B; Ji, H et al. (1999) Fatty acid oxidation affects food intake by altering hepatic energy status. Am J Physiol 276:R1046-53
Horn, C C; Addis, A; Friedman, M I (1999) Neural substrate for an integrated metabolic control of feeding behavior. Am J Physiol 276:R113-9
Horn, C C; Friedman, M I (1998) Metabolic inhibition increases feeding and brain Fos-like immunoreactivity as a function of diet. Am J Physiol 275:R448-59

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