Biomedical subjects

M I Friedman

Publications and source records attributed to M I Friedman.

At least 73 records · Page 4Linked to original sources

PubMed1989

Drinking saccharin increases food intake and preference--I. Comparison with other drinks.

To examine the orosensory and postingestive effects of saccharin solution on food intake and food preference, freely feeding rats were given flavored food to eat and a solution to drink for 2 h on eight to ten occasions. Relative to trials with a different flavored food and only water to drink, food intake was increased by drinking 0.2% saccharin or 0.45% NaCl, unaffected by drinking 1% almond extract, and decreased by drinking 10% glucose. Food preference, which was assessed in a choice test with simultaneous access to the two flavored foods, was increased by drinking 0.2% saccharin or 10% glucose and unaffected by drinking 1% almond extract or 0.45% NaCl. These results are consistent with the possibility that a combination of the oral and hydrational properties of saccharin solution increase food intake. Saccharin's sweet taste may be responsible for its effects on food preference.

Animals↗

PubMed1989

Drinking saccharin increases food intake and preference--II. Hydrational factors.

Rats that drink saccharin solution increase their short-term food intake and develop a preference for flavored food eaten when saccharin is ingested. In this paper, we examined whether these changes in feeding behavior were due to overhydration resulting from drinking hyposmotic saccharin solution. Consistent with this possibility, the short-term food intake of rats was increased by drinking hyposmotic 0.2% saccharin dissolved in water, unaffected by drinking isosmotic 0.9% NaCl, and decreased by drinking 0.2% saccharin dissolved in 0.9% NaCl. In addition, rats showed a sustained increase in saccharin-induced food intake after antidiuretic hormone treatment, which was designed to exacerbate their positive water balance. Less consistent with a hydrational explanation of saccharin-induced feeding was the finding that rats drinking only 2ml 0.2% saccharin solution increased food intake. Also, gastric intubation of similar volumes of water produced a small, transient increase in feeding behavior, which was apparent after the first intubation only and could not be preserved by adding water-contingent flavors to the food. Taken together, these results suggest that the hydrational effects of drinking hyposmotic saccharin solution contribute to, but cannot account for, the increase in food intake. Hydration had no observable influence on the acquisition of flavored food preference.

Animals↗

PubMed1989

Drinking saccharin increases food intake and preference--III. Sensory and associative factors.

Rats that drink saccharin solution increase their short-term food intake and develop a preference for flavored food eaten when saccharin is ingested. Here we describe experiments that examined whether these changes in feeding behavior were due to learning and/or the reinforcing sensory properties of saccharin solution. It was found that learning was unnecessary for the feeding response, as rats that drank saccharin increased food intake whether or not their food contained saccharin-contingent flavor cues. However, learning helped support and maintain the response, as rats repeatedly given flavored food together with saccharin to drink later increased intake when given the flavored food without saccharin (i.e. in extinction). The rewarding or hedonic effects of the immediate orosensory properties of saccharin were not responsible for its effects on feeding, as drinking saccharin before but not after eating flavored food increased food intake and food preference. Furthermore, hungry rats developed an aversion to flavored food paired with saccharin ingestion when the quantity of food was limited. This implies that the flavored food preference produced by drinking saccharin involves an association between sensory aspects of the food and the metabolic consequences of food ingestion, which interact with a postingestive action of drinking saccharin that is related to the rat's metabolic state.

Animals↗

PubMed1989

Drinking saccharin increases food intake and preference--IV. Cephalic phase and metabolic factors.

Rats that drink saccharin solution increase their short-term food intake and develop a preference for flavored food eaten when saccharin is ingested. In this paper, we examined whether these effects are mediated by cephalic-phase metabolic reflexes. The results show that the cephalic-phase insulin response could be dissociated from food intake in three ways. (1) Drinking saccharin increased the food intake and food preference of rats with sham surgery (SHM) or celiac vagotomy (CV), but not hepatic vagotomy (HV); it produced a short-lived increase in plasma insulin levels in all three groups, but the insulin response of both the CV and HV group was attenuated relative to the SHM group. (2) Rats increased food intake even when a 90 min interval was imposed between drinking saccharin and eating food, although insulin and glucose levels returned to normal within 30 min of drinking saccharin. (3) Streptozotocin-induced diabetes did not affect the increased feeding response to saccharin. The failure of rats given hepatic vagotomy to increase food intake and food preference when drinking saccharin suggests that a hepatic mechanism is involved. We propose that drinking saccharin increases food intake by temporarily altering the disposition of metabolic fuels towards storage and away from oxidation. Flavored food eaten after drinking saccharin becomes preferred because it provides fuel to counteract this reduction in oxidation.

Animals↗

PubMed1989

Assessment of right ventricular anatomy and function by quantitative radionuclide ventriculography.

Determination of right ventricular ejection fraction and volumes from radionuclide studies is cumbersome and is subject to considerable methodologic error. Further, assessment of regional wall motion has only infrequently been approached in a systematic way. A system of right ventricular ejection fraction and volume measurements is described that utilizes the previously validated single plane geometric method applied to first pass radionuclide angiocardiograms. Five right ventricular chords were defined and used to assess regional wall motion; normal values were obtained from 14 patients who were without demonstrable cardiac disease. Among 23 patients with anterior myocardial infarction, the right ventricular ejection fraction was within 2 SD of normal in 16; however, 3 of these patients showed regional wall motion abnormalities in the right ventricle. Of 21 patients with inferior myocardial infarction, right ventricular ejection fraction was reduced in 15; of the 6 with normal values, 3 had regional wall motion abnormalities as demonstrated by the chord shortening method. Of 21 patients with dilated cardiomyopathy, right ventricular function was abnormal in 20; the presence of a wall motion abnormality in the conus segment separated these patients from patients with right ventricular dysfunction after recent myocardial infarction. Thus: 1) right ventricular ejection fraction, volumes and wall motion can be assessed by a simple, geometric technique; 2) analysis of chord shortening by this method provides information unavailable from global ejection fraction data alone; and 3) the clinical correlates of these data will require further investigation.

Adult↗

PubMed1989

Effect of hepatic portal glucose concentration on food intake and metabolism.

To examine the effect of different hepatic portal glucose concentrations on food intake and metabolism, rats were given hepatic portal or jugular infusions (83 microliters/min for 2 h) of 0.3, 0.6, and 1.2 M glucose, equiosmotic NaCl, or a mock control infusion. Food intake was decreased to the same extent by the three concentrations of glucose infused into the hepatic portal vein and unaffected by any concentration of glucose infused into the jugular vein. Parallel to the changes in food intake, hepatic glycogen content was increased by glucose infused into the hepatic portal vein but not jugular vein. Conversely, systemic plasma glucose levels were increased by glucose infused into the jugular vein but not hepatic portal vein. Plasma insulin levels increased to the same extent irrespective of the route of infusion. Food intake was unaffected by the osmolarity of glucose infused into the hepatic portal vein, but was decreased by hyperosmotic NaCl control infusions. Hyperosmotic NaCl infusions also elevated levels of circulating fat fuels, indicating a stress response. The results show that the critical metabolic event in the liver that influences food intake is only indirectly coupled to the concentration of glucose in the hepatic portal vein.

Analysis of Variance↗

PubMed1989

Metabolic control of food intake.

A specific biochemical mechanism for the metabolic control of food intake has not been identified. However, a theory based on a signal generated from the oxidation of metabolic fuels and detected in the liver offers a powerful, integrative framework that helps explain a number of phenomena related to feeding behavior. In addition to providing a metabolic basis for the formation of conditioned food flavor preferences, a control of food intake by fuel oxidation provides a mechanism for overeating in the dynamic phase of obesity and hyperphagia produced by high-fat diets.

Feeding Behavior↗

PubMed1988

Contribution of fat metabolism to 'glucoprivic' feeding produced by fourth ventricular 5-thio-D-glucose.

We examined whether manipulations of fat metabolism influence the feeding response to peripheral or central administration of 5-thio-D-glucose (5-TG), a potent inhibitor of glucose utilization. The increase in food intake produced by peritoneal (50 mg/kg) or fourth ventricular (50, 100, 150 micrograms) 5-TG was potentiated by administration of the fatty acid oxidation inhibitor, methyl palmoxirate (10 mg/kg, p.o.). In addition, rats maintained on a high-fat diet ate less in response to fourth ventricular 5-TG (150 micrograms) than did rats maintained on an equicaloric low-fat diet. These results suggest that the feeding response to 'glucoprivation' is determined by the interaction of glucose and fat oxidation.

Animals↗

PubMed1988

Incidence of exertional right ventricular wall motion abnormalities in patients with coronary artery disease.

To evaluate the role of analysis of right ventricular function with exercise in patients with presumed coronary artery disease referred for radionuclide ventriculography, the records of 55 patients referred to our laboratory over a 19-month period were reviewed. All underwent rest and exercise first-pass radionuclide stress testing and cardiac catheterization within a period of four months. Three groups were identified: (1) patients with normal exercise right ventricular function (n = 24); (2) patients with exercise-induced right ventricular regional wall motion abnormalities (n = 15); and, (3) patients with abnormal resting right ventricular function without new exercise abnormalities (n = 16). Patients in each group were similar in age, sex, baseline left ventricular function, medication usage, and indication for study. The incidence of right coronary artery disease was identical in the three groups, as was the incidence of left ventricular functional abnormalities with exercise. Patients with proximal right coronary artery disease were more likely to have reduced left ventricular ejection fraction and more extensive coronary artery disease than those without disease at this site. We conclude that: (1) analysis of rest and exercise right ventricular function does not allow prediction of coronary anatomy in an unselected group of patients; (2) normal right ventricular function with exercise is compatible with extensive coronary artery disease, including proximal right coronary artery disease; and (3) abnormal exercise right ventricular function may be due to exertional left ventricular dysfunction in the absence of proximal right coronary artery disease.

Cardiac Catheterization↗

PubMed1988

Altered preferences for sucrose, sodium chloride, urea and hydrochloric acid solutions in an animal model of cholestatic liver disease.

Preferences for sucrose, sodium chloride (NaCl), urea and hydrochloric acid (HCl) solutions (representing sweet, salty, bitter and sour stimuli) were examined in rats with bile duct ligation using 24-hr two-bottle choice tests. Preferences in bile duct ligated rats for sucrose and NaCl solutions were decreased relative to control animals in the initial stages following ligation (Days 1-5) and then increased in the later stages (Days 11-20). Preferences for both HCl and urea solutions were decreased briefly compared to control animals but showed no consistent pattern. The results provide the first demonstration for altered ingestive behavior in an animal model of liver disease and suggest that the bile duct ligated rat may be useful in studying mechanisms of chemosensory disturbances in human liver disease.

Animals↗

PubMed1988

Sodium chloride preference is altered in a rat model of liver disease.

Rats with ligation of the common bile duct were used to study the effect of liver disease on preferences for sodium chloride solutions. Preferences for NaCl were assessed by 24-hr two-bottle choice (preference) tests in both bile duct ligated (BDL) and control animals. Bile duct ligated animals showed greater preferences for 200 and 300 mM NaCl than either free-feeding or pair-fed control animals. In rats provided with continuous access to a single concentration of 200 mM NaCl both pre- and postligation, BDL animals showed an abrupt change in NaCl preference at day 12 postligation, while control animals showed no alterations in preference during the same time period. The results provide additional support for a role of the liver in determining NaCl solution preference and suggest that the BDL rat may be a useful model for the study of altered gustatory function in liver disease.

Animals↗

PubMed1988

Role of fatty acid oxidation in food intake and hunger motivation in Syrian hamsters.

We examined the metabolic control of food intake in Syrian hamsters using methyl palmoxirate (MP), an inhibitor of fatty acid oxidation. If fatty acid oxidation plays a role in the control of food intake in hamsters, as it does in rats, it would be expected that hamsters predisposed toward lipid metabolism would increase food intake in response to inhibition of fatty acid oxidation. To the contrary, female hamsters fed a high-fat diet for several weeks and then treated with MP (0.25-100 mg/kg) did not increase food intake relative to vehicle-treated controls. Furthermore, MP treatment did not enhance food intake in hamsters that had been previously food deprived for 12 hr. Consistent with the inhibition of fatty acid oxidation, plasma levels of total ketone bodies and glucose in the MP-treated hamsters were significantly lower than those of the vehicle-treated controls. Thus, treatment with doses of MP which apparently inhibited fatty acid oxidation did not enhance food intake, even after manipulations which predispose the hamsters toward utilization of fat fuels. The control of food intake in Syrian hamsters is in marked contrast to that of rats and other mammals in which the consequences of glucose and fat metabolism interact to signal changes in food intake.

Animals↗

PubMed1988

Ingestion of low concentrations of sucrose or hydrochloric acid solutions accelerates mortality in rats with cholestatic liver disease.

Mortality rates were monitored in bile duct ligated (BDL) rats which were consuming flavor solutions in addition to water and chow. Following ligation of the common bile duct, animals were offered a single concentration of a flavor solution (200 mM NaCl; 400 mM sucrose; 100 mM urea; 5 mM HCl) in addition to water. During three weeks postligation, mortality rates were compared between groups of ligated animals consuming either one of the taste solutions or consuming only water. Within the first five days postligation, mortality was 70% in ligated animals drinking HCl and 50% in animals consuming sucrose, compared to 30% for urea, 10% for sodium chloride and 0% in animals drinking only water. Total mortality of ligated rats consuming HCl or sucrose solutions was significantly increased compared to animals consuming only water. The results suggest that consumption of low concentrations of sucrose or HCl solutions during the initial stages of liver disease in BDL rats may drastically accelerate their mortality rate.

Animals↗

PubMed1988

Macronutrient selection in an animal model of cholestatic liver disease.

Diet selection was investigated in an animal model of cholestatic liver disease produced by bile duct ligation. Animals self-selected diets from separate sources of macronutrients (protein, fat, carbohydrate). Diet selection was evaluated when the fat source was comprised of either a primarily medium-chain fat (coconut oil) or a primarily long-chain fat (Crisco vegetable shortening). Relative to intakes of control animals, bile duct ligated (BDL) animals consuming the long-chain fat decreased fat intake, decreased protein intake, and increased carbohydrate intake. Consumption of the fat source was decreased in BDL rats fed the medium-chain fat relative to intakes of control animals, however carbohydrate and protein intakes were not affected. Total caloric intake was comparable to control intakes by day 16 post-ligation in BDL rats fed the long-chain fat and by day 11 in BDL rats fed the medium-chain fat. Body weight gain was significantly greater in BDL rats fed the medium-chain fat than in those fed the long-chain fat. Mortality was 44% in BDL animals fed the long-chain fat, and 0% in those fed the medium-chain fat. The results suggest that BDL animals make dietary selections which may decrease the severity of liver disease. Differences between ligated animals consuming either medium- or long-chain fats suggest that some fat sources may be more beneficial during cholestasis.

Alkaline Phosphatase↗

PubMed1988

Daily caloric intake of normal-weight adults: response to changes in dietary energy density of a luncheon meal.

The extent and time course of caloric compensation for surreptitious dilutions and supplements to the energy value of the diet were examined in free-living normal-weight adults. Ten subjects were provided lunches containing approximately 66% more or less calories than their customary midday meal for 2-wk periods which were interposed between 1-wk baseline or recovery periods. Diet records were kept throughout the study. Total energy intakes did not differ among the three control periods (weeks 1, 4, and 7) or between any of these periods and when subjects were provided the low-calorie meal. Total energy intake was significantly higher relative to all other periods when subjects ingested the high-calorie meal. To the extent that compensation occurred, it was apparent immediately and did not appear to change over the 2-wk study periods. The results suggest that humans compensate more readily for decreases than for increases in caloric intake.

Adult↗

PubMed1988

2,5-anhydro-D-mannitol: a fructose analogue that increases food intake in rats.

We examined the effects on food intake and plasma fuels of 2,5-anhydro-D-mannitol (2,5-AM; 2-deoxy-D-fructose), a fructose analogue that inhibits hepatocyte gluconeogenesis and glycogenolysis in vitro. 2,5-AM (50-800 mg/kg po) given to rats during the diurnal fast produced a dose-related increase in food intake during the 2 h after administration. A 200-mg/kg dose of 2,5-AM decreased plasma glucose, increased plasma ketone bodies, free fatty acids, and glycerol, and had no effect on triglycerides. Normal and diabetic rats given 2,5-AM (200 mg/kg ip) increased food intake to the same extent. These results suggest that, unlike other substrate analogues that increase food intake, 2,5-AM increases feeding by creating a metabolic state that resembles fasting.

Animals↗

PubMed1988

Hepatic control of feeding: effect of glucose, fructose, and mannitol infusion.

Plasma fuels, pancreatic hormones, liver glycogen, and food and water intake were measured immediately before or during the nocturnal feeding period of rats given hepatic portal or jugular infusions of glucose, fructose, and mannitol (0.3 M x 10 ml/2 h). Compared with mock and saline control infusions, hepatic portal glucose, fructose, and mannitol reliably and equally decreased food intake. Jugular fructose and mannitol also decreased food intake when infused before rats ate but not while they ate. Jugular glucose infusion did not affect food intake. Hepatic portal glucose did not reliably elevate systemic plasma glucose or insulin but increased hepatic glycogen content, indicating that most infused glucose was taken up by the liver. In contrast, jugular glucose increased systemic plasma glucose and insulin but did not affect hepatic glycogen. Hepatic portal fructose decreased plasma ketones and increased triglycerides and liver glycogen. Jugular fructose also decreased ketone levels and tended to increase liver glycogen. Mannitol by either route decreased plasma glucose and increased plasma free fatty acids. These results indicate that hepatic portal infusions that produce changes in plasma fuel concentrations within the physiological range decrease food intake. They strongly suggest this is accomplished by a direct action of the infusates on the metabolism of the liver.

Animals↗

PubMed1988

Satiating effect of fat in diabetic rats: gastrointestinal and postabsorptive factors.

Streptozotocin-diabetic rats decrease food intake more than normal animals in response to a fat test meal. To determine the physiological basis of this differential response, we examined the effects of an ingested corn oil meal on food intake, gastrointestinal fill, and plasma triglycerides, glycerol, and ketone bodies. Hyperphagic diabetic rats decreased intake of a high-carbohydrate, low-fat stock diet starting 2-4 h after the fat meal, whereas normal rats did not. Gastric emptying was accelerated and intestinal mass and contents were increased in diabetic rats. The fat meal reduced gastric emptying and increased stomach contents in diabetic and normal rats starting within 2 h of ingestion. Intestinal fill decreased in diabetic animals after the oil meal. Triglycerides and glycerol increased transiently after fat ingestion in normal and diabetic rats, whereas ketone body concentrations rose only in diabetic rats starting 1-3 h after fat ingestion. The results indicate that the differential effect of a fat meal on food intake in normal and diabetic rats is related to differences in the postabsorptive metabolism of the ingested fat rather than to effects of fat feeding on gastrointestinal fill or clearance.

Animals↗