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Biomedical subjects

M I Friedman

Publications and source records attributed to M I Friedman.

At least 91 records · Page 5Linked to original sources

Food flavor preferences produced by drinking glucose and oil in normal and diabetic rats: evidence for conditioning based on fuel oxidation.

Free-feeding normal and streptozotocin-diabetic rats were allowed to drink 10 ml of 35% glucose solution or an equicaloric 15% corn oil emulsion during the 1st hr of the dark period. While the drinks were available, the rats ate food that contained distinctive flavors such that a particular flavor was always associated with a particular drink. It was found that relative to a control flavored food given without a nutritive drink, (1) flavored food consumed with a glucose solution was preferred by normal rats but avoided by diabetic rats, and (2) flavored food consumed with an oil emulsion was preferred by both normal and diabetic rats. When given a choice between one flavored food paired with drinking glucose and another flavored food paired with drinking oil, normal rats showed no preference but diabetic rats preferred the oil-paired flavored food. These results can best be explained by consideration of the different ability of normal and diabetic rats to oxidize glucose.

Animals↗

Insulin counteracts the satiating effect of a fat meal in rats.

The effects of insulin administration of the reduction on food intake which follows a meal of corn oil was examined in normal and streptozotocin-diabetic rats. In the first experiment, a single injection of long-acting, protamine zinc insulin (3 IU) curtailed the decrease in 24-hr food intake that occurred in normal and diabetic rats after ingestion of 2.0 ml of oil. In a second experiment, injection of short-acting, regular insulin (0.5 IU) prevented the depression of food intake which occurred 6-24 hr after ingestion of 1.5 ml of corn oil, but not at earlier time intervals. In a third experiment, the short-term suppression of food intake in diabetic rats that occurred within 6 hr after a 1.5 ml meal of oil was reduced by chronic administration of insulin (3 IU/day) via a subcutaneously implanted osmotic pump. The results indicate that a relatively long-lasting effect of insulin counteracts the satiation from ingested fat and suggest that insulin's role in the control of food intake may depend on the composition of the diet.

Animals↗

Further evidence for hepatic control of salt intake in rats.

We examined the contributions of oral and hepatic factors to the control of salt intake in rats made "salt hungry" by combined dietary sodium restriction and furosemide treatment. A 7.5-ml preload of 0.5 M NaCl, which was either voluntarily ingested or slowly infused (7.5 ml/90 min) into the hepatic portal vein, decreased subsequent 0.5 M NaCl intake by approximately 7.5 ml in both cases. Hepatic portal infusions were probably acting in the liver because slow jugular infusions (7.5 ml/90 min) did not influence salt drinking, although rapid (7.5 ml/5 min) infusions by both routes reduced salt intake. If salt was ingested but drained through a gastric cannula, rats showed little sign of reducing salt in a 2-h test. These results suggest that the quantity of salt ingested by salt-hungry rats is regulated by a postabsorptive mechanism that is probably located in the liver.

Administration, Oral↗

The effect of diet on food intake and adiposity in rats made obese by gestational undernutrition.

Undernutrition limited to the first two weeks (trimesters) of pregnancy in rats produces a delayed-onset enhancement of body weight and food intake in male but not female offspring. Adiposity measures (fat cell size, fat pad weight and carcass lipid content) however, were enhanced only in male offspring of previously deprived mothers maintained on a high-fat diet. Previous work had shown that although these adiposity differences are enhanced by this diet, hyperphagia was eliminated when animals were switched to the high-fat diet as adults. The current study demonstrates that if offspring of deprived animals are exposed to the high-fat diet early in life, hyperphagia ensues. Adipocyte number, and circulating triglyceride levels were unaffected by our nutritional manipulation.

Adipose Tissue↗

Integrated metabolic control of food intake.

Inhibition of glycolysis and fatty acid oxidation by combined treatment with 2-deoxyglucose (2DG) and methyl palmoxirate, or inhibition of glycolysis and lipolysis by combined treatment with 2DG and nicotonic acid synergistically increased food intake in rats. Methyl palmoxirate treatment alone increased food intake in rats fed a high-fat, but not low-fat diet. These results provide direct evidence for a mechanism in the control of food intake that integrates signals generated by the metabolism of glucose and fatty acids. In addition, they strongly indicate a role for fatty acid oxidation in the control of eating and raise the possibility that an interaction between glucose and fat metabolism underlies the link between regulation of body fat stores and short-term food intake.

Animals↗

Hepatic portal glucose infusions decrease food intake and increase food preference.

We examined the contribution of experimental factors to the hepatic control of food intake. Rats with either hepatic portal or jugular catheters were infused four times with glucose (4.5 mg/min) and equitonic saline (2 ml/2 h). During the infusions their food contained nonnutritive chocolate or chicken flavor, depending on the infusate received. Hepatic portal glucose decreased food intake relative to saline and no infusion conditions, but jugular glucose did not. When allowed to choose between the flavors associated with each infusate, rats with hepatic portal catheters preferred the flavor eaten during glucose infusion, and rats with jugular catheters showed no preference. These results suggest that a mechanism located in the liver can reduce food intake without producing malaise and that portal glucose can act as an unconditioned stimulus for the acquisition of a learned food preference. Several reports that hepatic portal infusions do not alter feeding behavior may be explained by a failure to control for previous experience in the test situation.

Animals↗

Fatty acid oxidation and glucose utilization interact to control food intake in rats.

To determine whether glucose and fat metabolism interact to control food intake, rats were administered 2-deoxyglucose (2-DG), which inhibits glucose utilization, and methyl palmoxirate (MP), which inhibits fatty acid oxidation. Combined treatment with 2-DG and MP increased food intake in a synergistic fashion. This synergistic effect was observed even at doses of the two agents that alone did not increase food intake, and it was expressed by either an initiation of eating or a prolonged bout of eating, depending on the testing conditions. Metabolic measures of circulating substrates, liver glycogen, and gastric contents confirmed that the drugs had their intended metabolic effects and revealed no evidence that one drug enhanced the direct metabolic action of the other. The results provide direct evidence that glucose and fat metabolism exert a coordinated control over feeding behavior and suggest the existence of a common integrative mechanism in that control.

Animals↗

Hepatic contribution to satiation of salt appetite in rats.

We examined the influence of hepatic-portal vein infusion of NaCl and of hepatic vagotomy on 3% NaCl solution drinking by sodium-deficient rats. Combined dietary sodium restriction and administration of the natriuretic agent, furosemide (5 mg), produced a vigorous appetite for 3% NaCl solution that was attenuated by portal infusion of NaCl. Whereas infusions (1 ml/30 min) of NaCl into the hepatic-portal vein in concentrations as low as 0.15 M (isotonic) significantly reduced 3% NaCl consumption, a higher concentration (0.6 M) infused into the jugular vein, or portal infusions of KCl (0.6 M) or sucrose (1.2 M), were ineffective. Rats with selective hepatic vagotomy displayed an attenuated appetite for salt whether or not they received hepatic-portal NaCl. This was not due to altered excretion of sodium. Taken together, these results suggest that the liver or portal vein can provide a sodium-specific neural signal capable of attenuating the appetite for salt and this information is transferred to the brain by fibers in the hepatic vagus that fire in reciprocal relationship with portal sodium concentration.

Animals↗

Relationship of fat metabolism to food intake.

A model for the role of body fat stores in the control of food intake is outlined. It is proposed that changes in the storage and mobilization of fuels into and from adipose tissue affect food intake indirectly by altering the supply of utilizable metabolic fuels. Experiments are reviewed in which this hypothesis is tested by an examination of the hypophagia that occurs following termination of obesity-producing injections of insulin. The results indicate that whereas excess mobilization of fat from adipose tissue does not entirely account for postinsulin hypophagia, changes in hepatic liquid metabolism may be a factor. It is proposed that the satiating effects of fat from either endogenous or exogenous sources may depend on the degree to which lipids are oxidized.

Adipose Tissue↗

Food intake in diabetic rats: isolation of primary metabolic effects of fat feeding.

The effects of varying dietary fat content on food intake and metabolism in streptozotocin-diabetic rats were examined. The metabolic consequences of fat feeding were separated from the marked adjustments in voluntary food consumption that occur when diabetic rats are fed diets containing different amounts of fat by feeding rats a fixed ration of food in which either fats or carbohydrates were reduced by equicaloric amounts, or in which only the concentration of fat, but not other dietary nutrients, was varied systematically. Resulting changes in metabolism and subsequent ad libitum food intake on refeeding were then measured. Rats did not increase their food intake after a prior reduction in carbohydrate consumption but did so after an equicaloric reduction in fat consumption. Urinary glucose excretion during rationing was a function of carbohydrate consumption and was not predictive of changes in food intake during refeeding. The more fat that rats consumed during rationing, the higher their levels of plasma triglycerides and ketone bodies were at the time of refeeding and the less they ate when allowed to eat ad libitum. The orderly changes in food consumption and in plasma triglycerides and ketones observed with variations in fat intake suggest that the effects of fat feeding on food intake in diabetic rats are mediated through the oxidation of ingested fat.

Animals↗

First-third ejection fraction: is the first-pass radionuclide method accurate?

Previous reports have suggested that left ventricular first-third ejection fraction (EF) can be obtained from the left ventricular time-activity curve derived from first-pass radionuclide angiography based on Anger camera data. The validity of this technique was assessed by: a study of beat-to-beat variations in data from 15 patients in which electrocardiographic data were simultaneously recorded, and a computer simulation incorporating the application of Poisson statistics to appropriate count rate data. The results of patients studies showed no consistent trend in any first-third parameter obtained from consecutive beats in individual subjects, and unacceptably high statistical uncertainty in the calculation of the first-third ejection fraction. The weighted standard deviation of the first-third ejection fraction in each of 15 patients studied averaged 7.5 EF units, while first-third ejection fraction averaged 22.9 EF units. The relative error averaged 32%. The computer simulation indicated a high relative error of 47% associated with the first-third ejection fraction at typical end-diastolic count rates of 200 per frame from 1,000 computer Poisson randomizations of an appropriate analog volume curve. The results render the first-pass radiocardiographic method invalid for determining first-third ejection fraction.

Adult↗

Effect of hepatic vagotomy and/or coeliac ganglionectomy on the delayed eating response to insulin and 2DG injection in rats.

The eating response that occurs following recovery from the effects of insulin or 2-deoxy-D-glucose (2DG) injection was examined in rats with hepatic vagotomy and/or coeliac ganglionectomy. Rats were deprived of food and injected with either saline (1 ml/kg), regular insulin (3 U/kg) or 2DG (200 mg/kg). Plasma glucose was measured periodically over the next 6 hr and then food was returned and intakes were measured over the next 2 hr. Rats increased food intake 6-8 hr after insulin or 2DG injection compared to the saline (control) condition. Nerve section did not affect the plasma glucose or food intake responses to insulin or 2DG injection. The results indicate that the innervation of the liver via the vagus nerve or coeliac ganglion is not involved in the delayed eating response to insulin and 2DG injection.

Animals↗

Response of normal and diabetic rats to increasing dietary medium-chain triglyceride content.

Replacing dietary long-chain triglycerides (LCT) with medium-chain triglycerides (MCT) has not previously been shown to produce reliable changes in caloric intake. However, diabetic rats are particularly sensitive to changes in the fat content of their diet, and thus were used for comparison to normal rats in the studies reported below. Rats were fed synthetic diets that contained either corn oil or MCT. Food intake and plasma metabolic fuels were measured as the fat content of the diet was increased from 5 to 15 to 25%. Both normal and diabetic MCT-fed rats adjusted their caloric intake more quickly than LCT-fed rats as the fat content of the diet was increased. The relative preference of MCT- and LCT-fed rats for high and low concentrations of dietary fat was assessed. It was found that both normal and diabetic LCT-fed rats preferred high dietary fat, whereas MCT-fed rats did not. In normal rats, plasma triglycerides and glycerol were decreased and plasma ketones increased by MCT feeding. In diabetic rats, the only effect of MCT feeding was to decrease plasma glycerol and triglycerides. The relative importance of hedonic and metabolic feedback to the rapid caloric regulation of MCT-fed rats is discussed.

Animals↗

Gestational undernutrition and the development of obesity in rats.

The effects of early gestational undernutrition and subsequent refeeding patterns on offspring food intake, body weight and adiposity were examined. Pregnant rats were food restricted to 50% of their preconception intake levels during the first 2 weeks of pregnancy and were then either returned to ad libitum feeding or pair-fed to nonrestricted control rats. Male and female offspring of previously deprived, ad libitum refed mothers gained significantly more weight when fed a standard low fat, high carbohydrate diet than did control offspring. When the maintenance diet was changed at 140 days of age to a high fat diet, both groups of previously deprived male offspring gained weight at greater than control rates. In contrast, the three groups of female rats gained weight at comparable rates after the diet change. Adipocyte hypertrophy and elevated carcass lipid content were seen in high fat-fed male but not female offspring of previously deprived mothers. Adipose tissue lipoprotein lipase activity was unaffected by these manipulations.

Adipose Tissue↗

Evidence for hepatic involvement in control of ad libitum food intake in rats.

Sectioning the hepatic branch of the anterior abdominal vagal trunk attenuated but did not abolish the normal nocturnal bias in the day-night distribution of food intake in female rats. Neither total daily food intake nor body weight was affected by hepatic vagotomy. This effect appeared to be specific to the hepatic branch of the nerve because sectioning the remaining (gastric and celiac) abdominal vagal branches did not influence daily feeding rhythms and appeared to be specific to feeding behavior, because the day-night rhythms of drinking behavior and wheel-running activity were not affected by hepatic vagotomy. In male rats, hepatic vagotomy also produced an increase in daytime food consumption but without commensurate reduction in nighttime eating. As a result, male rats with hepatic vagotomy displayed a modest chronic hyperphagia and body weight gain, which was associated primarily with increased linear growth. The effect of nerve section on daytime food intake was expressed quite rapidly. Daytime food intake increased within 8 h after hepatic vagotomy, which was produced at light onset by pulling on a previously implanted suture. Collectively, these results demonstrate that hepatic vagotomy changes daily feeding rhythms and suggest that the liver and perhaps its vagal innervation are involved in the control of ad libitum eating behavior.

Animals↗

Measurement of regional myocardial perfusion using collimated miniature radiation detectors and the method of 133-xenon washout.

A new approach to the measurement of local myocardial perfusion based on the application of highly-collimated miniature cadmium telluride radiation detectors to measure washout of 133-Xenon from well-defined tissue volumes is presented. Single-hole collimators with length/diameter ratios of 1 (L = 4 mm, D = 4 mm) and 4 (L = 12 mm, D = 3 mm) were employed as prototype designs. The probe field of view was characterized theoretically using a spherical model of the myocardium in conjunction with experimental point source response measurements for each collimator. Method evaluation using two medium resolution collimators (L/D = 1) was effected by performing left main and circumflex coronary artery perfusion studies at controlled but variable flows in the dog heart. An excellent correlation (r greater than 0.99) between actual and estimated perfusion determined from 65 washout curves over the flow range 0.38 to 3.18 ml/min/gm was demonstrated. The ability to resolve regional flow differences was verified by measuring tracer washout from circumflex and left anterior descending regions of the myocardium, using two high resolution collimators (L/D = 4), in a preparation where the left main coronary artery was cannulated and a snare was placed around the circumflex coronary artery to selectively reduce flow to that region.

Biomedical Engineering↗