1985 — 1987 |
Friedman, Mark |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Role of Metabolic Fuels in the Control of Food Intake @ Monell Chemical Senses Center
Of the two major classes of metabolic fuels, glucose and lipids, more research has been done on the role of glucose in the control of eating behavior. There is substantial evidence that dietary and endogenous fats modify eating in rats. However, while it is known that alterations in the intracellular utilization of glucose provide a signal controlling food intake, much less is known about the mechanism of action of lipids. Numerous observations suggest that oxidation of fat fuels provide a signal controlling food intake. We plan to examine this relationship further by studying the effects on food intake of dietary fats, administration of pure fat and fats mobilized from internal reserves in normal and diabetic rats. Measurements of plasma metabolic fuels will help to characterize metabolic effects and will provide indices of fat oxidation. The role of fat fuel oxidation in the control of eating will be tested by assessing quantitative relationships between metabolic changes and food intake. By varying the type of fat used, by manipulating metabolism with insulin treatment and by pharmacologic inhibition of fatty acid oxidation. These studies should provide basic information on metabolic factors involved in the control of food and caloric intake.
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0.915 |
1985 — 1988 |
Friedman, Mark |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Postabsorptive Control of Food Intake in Humans @ Monell Chemical Senses Center
Food intake in humans is often thought to be under the control of sociocultural, cognitive, sensory and other external factors. Physiological factors controlling food intake are usually not emphasized in explanations of human eating behavior. There is evidence that food intake in humans may be under a postabsorptive control responsive to the availability and metabolism of circulating nutrients; however, because of various methodological limitations this evidence is not conclusive. Based on the results of preliminary studies, we proposed experiments to examine the effect of intravenous feeding on food intake in healthy male volunteers. One aspect of these studies will involve an examination of subject-and experiment-related factors which affect food intake under our experimental conditions. We will also determine whether the compensatory reduction in voluntary food intake observed during intravenous feeding is a response to specific nutrients or a response to calories. The restoration of food intake after cessation of intravenous feeding will be examined with respect to time course and role of prior nutrient infusion. We will also determine whether intravenous feeding reduces intake of a normal, varied diet as it does a liquid diet. Finally, we will determine whether subjects can maintain caloric intake by self-administration of intravenous nutrients. These studies will provide basic information on the postabsorptive control of food intake in humans. In addition, these experiements may help to explain problems in appetite and difficulties in the transition from intravenous to oral feeding in patients recieving parenteral nutrition.
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0.915 |
1993 — 2005 |
Friedman, Mark |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Metabolic Control of Feeding Behavior @ Monell Chemical Senses Center
This is a request for five additional years support to carry out experiments involving metabolic subcellular changes in the liver and how they influence the onset of meals in rats. Prior evidence produced by the investigator suggests that when food intake is initiated after the administration of the metabolic inhibitor, 2, 5-AM, there are several correlates in hepatocytes that may well have a causal role. More specifically, the results of several types of experiments have converged to strongly implicate that the liver is the target for 2, 5-AMs or exigenicaction; and other experiments have indicated that a key factor (or at least close correlate) is a reduction in the amount of ATP in hepatocytes. Proposed experiments will take the analysis to a more reductionistic level by assessing whether bound or free cellular ATP is more correlated with eating and by then determining if a reduction in the key ATP pool elicit seating when induced by other means; will determine if other drugs thought to elicit eating via the liver (e.g., methyl palmoxirate) are associated with similar hepatocyte changes; will assess the hypothesis that the signal to eat is associated with functioning of the hepatocyte sodium pump; and will determine if changes in hepatocyte calcium pools are a means for generating a signal that could pass from hepatocytes to other cells and on the CNS.
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0.915 |
1994 — 1996 |
Friedman, Mark Teeter, John Wysocki, Charles [⬀] Kalinoski, D. Lynn Restrepo, Diego |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Microscopy in the Chemical Senses @ Monell Chemical Senses Center
This group proposal seeks funds to purchase three major items of equipment: a cryostat, a compound, research-grade microscope and a confocal microscope. These items will be housed in the Histological Facility at the Monell Chemical Senses Center and will be utilized Center-wide. The equipment is requested by eight major users for research programs directed at a fuller understanding of the chemical senses. The projects utilize standard histology, lectin and immuno-histochemistry, in situ hybridization and in situ PCR, and focus on a range of issues from intracellular localization of proteins and neucleotides in peripheral sensory receptor cells to metabolic activity within large organ systems, e.g. the brain and the liver.
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0.915 |
1995 — 2003 |
Friedman, Mark |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Hepatic Mechanism For Control of Food Intake @ Monell Chemical Senses Center
DESCRIPTION (Adapted From The Applicant's Abstract): 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.
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0.915 |
2000 |
Friedman, Mark |
F06Activity Code Description: Undocumented code - click on the grant title for more information. |
Sensory Function of the Liver in Emesis @ Monell Chemical Senses Center
Nausea and vomiting compromise the health and quality of life of patients with a variety of diseases, and create an obstacle to compliance with treatments that produce these disturbing side effects. Nausea and vomiting can be triggered by appropriate stimulation of several sites in the body, including the gastrointestinal tract and area postrema in the brainstem. The purpose of this project is to determine whether emetic agents and mediators also act in liver to generate a neural signal that triggers vomiting (emesis). Using the ferret, a standard animal model for studies the emetic reflex, we will: (1) Determine whether cyclophosphamide, which is used in cancer chemotherapy, acts in liver to induce emesis by comparing the effects of hepatic portal and jugular (systemic) infusion of different doses of this drug. (2) Determine whether the emetic mediator, 5-hydroxytryptamine (5HT) acts in liver to induce vomiting by comparing the effects of hepatic portal and jugular infusion of different concentrations of 5HT. (3) Investigate whether vagal sensory neurons transmit a hepatic signal for emesis by severing the nerves between the liver to brain. The results of this work should contribute to our knowledge of the mechanisms of nausea and vomiting, and may lead to the development of better treatments for these conditions.
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0.915 |