Feeding behavior is controlled in part by post-absorptive fuel metabolism. In order for fuel metabolism to affect feeding, the brain must be informed. The liver monitors fuel metabolism and generates signals that the brain uses to control feeding behavior. The overall goal of this project is to understand the operation of this hepatic control of food intake. The experiments proposed in this application will provide important information about hepatic mechanisms that control feeding behavior, and thus will contribute to a fuller understanding of the etiology of overeating, obesity and anorexia, and to the development of appropriate strategies for their prevention and treatment.
Two aims of this project pertain to the neural substrate for the transmission and processing of the hepatic hunger signal(s). Experiments will be performed to: 1) locate the neurons involved in the transmission and processing of hepatic metabolic hunger signals; and 2) determine where different peripheral metabolic hunger signals are integrated to control feeding behavior.
Three aims of the project address questions concerning the hepatic mechanism that mediates satiety in glucose and fat. To address these issues experiments will be conducted to determine whether: 1) the difference in glucose concentration in the blood vessels supplying the liver (hepatic artery and hepatic portal vein) generates a satiety signal; 2) the sensory neurons in the vagus nerves mediate the satiating effect of high concentrations of hepatic portal vein glucose; and 3) the satiating effect of fat is due to its metabolism in the liver. Another aim of this project pertains to which cell types in the liver are the source of hepatic signals that control feeding behavior. To address this, an experiment will be performed to determine whether a metabolic hunger signal originates from hepatocytes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK036339-13
Application #
2853009
Study Section
Special Emphasis Panel (ZRG1-IFCN-1 (01))
Program Officer
Yanovski, Susan Z
Project Start
1986-01-01
Project End
2004-03-31
Budget Start
1999-05-01
Budget End
2000-03-31
Support Year
13
Fiscal Year
1999
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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