Dietary practices in obesity.
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Biomedical subjects
Publications and source records attributed to F X Pi-Sunyer.
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The satiety effect of cholecystokinin (CCK) that was first observed in rats has now been extended to chickens, rabbits, pigs, sheep, rhesus monkeys, lean mice, genetically obese mice and rats, neurologically obese rats, lean men and women, and obese men. The effect is specific and can be obtained in animals and humans without reports or signs of sickness. The mechanism of the effect is unknown, but the gastric vagal fibers are necessary for the effect. This has led to the hypothesis that the satiety effect is due to activation of vagal afferent fibers that inhibit the central control system of feeding by CCK acting directly on recently described vagal CCK receptors and/or indirectly through a gastric smooth muscle effect that vagal receptors are sensitive to.
In comparison with a saline infusion, the infusion of the C-terminal octapeptide of cholecystokinin (4 ng/kg/min) decreased food intake by an average of 122 g in a group of 12 lean men without objective evidence of untoward side effects. Shapes of the cumulative intake curves under the two conditions were similar, but subjects ate less and stopped eating sooner when receiving octapeptide than when receiving saline. These results are consistent with the hypothesis that cholecystokinin is an endogenous signal for postprandial satiety. The results offer promise for the possible use of the octapeptide as an appetite suppressant.
The ability of pancreatic islets implanted into abdominal muscle to effect a recovery from streptozotocin-induced diabetes was compared with that of i.p implants. Pancreases from 17 to 35 Lewis neonates were cultured for 6 days and placed in i.m. or i.p. sites in severely diabetic Lewis rats. Body weight, food and water intakes, urinary output, and 4-hr fasted plasma glucose levels returned to normal in both groups. Neither plasma insulin and glucose responses to intravenous glucose tolerance tests nor plasma glucose responses to oral glucose tolerance tests differed among i.m. or i.p. implant recipients and normal, age-matched controls, even after 1 week's prior challenge of insulin secretory capacity by a high sucrose diet. Plasma glucose levels were reduced after oral administration of tolbutamide in the three groups. Plasma glucagon of i.m. and i.p. implant recipients after a 4-hr fast or after an oral load of arginine were not significantly different from those of controls, although levels tended to be higher in the implant groups. Neither i.m. nor i.p. implant groups reverted to the diabetic state in the 10 months following pancreatic implantation. These findings validate the long-term efficacy of intramuscular implantation of cultured islets in reversing diabetes in inbred rats.
A decreased capacity for fatty acid synthesis is associated with a decreased insulin effect on glucose metabolism in large fat cells and fat cells from rats fed a high-fat diet. We have investigated the relationship between these processes by specifically inhibiting fatty acid synthesis with (-)-hydroxycitrate (2.5 mM), an inhibitor of citrate cleavage enzyme, and cerulenin (0.05 mM), an inhibitor of fatty acid synthetase. (-)-Hydroxycitrate and cerulenin decreased maximally insulin-stimulated fatty acid synthesis from [6-(14)C]glucose to 10% and 25% of controls, respectively, while only (-)-hydroxycitrate decreased basal values. Oxidation of [1-(14)C]glucose in the presence of insulin was markedly depressed by each inhibitor. Thus, the percent increase over basal value was decreased from 540% in controls to 151% and 154% by (-)-hydroxycitrate and cerulenin, respectively. In contrast, oxidation of [6-(14)C]glucose was slightly enhanced by both inhibitors. Thus, oxidation of glucose via the pentose shunt was reduced, while Krebs cycle oxidation was unaffected. Basal and insulin-stimulated incorporation of [1-(14)C]glucose and [6-(14)C]glucose into glyceride-glycerol and basal lactate production was unchanged by the inhibition of fatty acid synthesis. Insulin-stimulated lactate production was halved by the inhibition of fatty acid synthesis. Total glucose utilization, as assessed by measuring the disappearance of glucose from the medium, was not detectably changed by inhibiting fatty acid synthesis under basal conditions, but insulin-stimulated values were decreased to 52% and 64% of control by (-)-hydroxycitrate and cerulenin, respectively. This occurred despite the fact that neither agent affected the initial rate of 2-deoxyglucose uptake, or glucose-6-phosphate dehydrogenase or 6-phosphogluconate dehydrogenase activities. These data therefore provide direct evidence that a limitation of the fatty acid synthetic pathway decreases the ability of insulin to stimulate both pentose shunt glucose oxidation and overall glucose utilization, but not Krebs cycle oxidation or glyceride-glycerol synthesis. The enzymatic capacity of the fat cell for fatty acid synthesis is therefore an important determinant of insulin-stimulated glucose utilization.-Fried, S. K., M. Lavau, and F. X. Pi-Sunyer. Role of fatty acid synthesis in the control of insulin-stimulated glucose utilization by rat adipocytes.
Obese individuals maintained for 64 days on either of two low-calorie diets (600-800 kcal/day), consisting of protein alone or protein plus carbohydrate, varied widely in the extent of their cumulative nitrogen deficits. Rates of weight loss showed little correlation with rates of nitrogen loss after the first 28 days of the study. The low-calorie diet consisting entirely of protein increased blood beta-hydroxybutyrate concentrations far more than did a diet consisting of equal parts of protein and carbohydrate. The diet which consisted almost entirely of protein did not spare body protein better or induce a greater rate of weight loss than did the mixture of protein and carbohydrate.
Culture of islets isolated from the pancreas of neonatal rats successfully preserved function for 6 days, as indicated by release of insulin into the culture medium and reversal of experimental diabetes bu cultured islet isografts. Release of insulin into the culture medium correlated with lowering of fasting blood glucose in the diabetic recipient. Intravenous glucose tolerance was normal in recipients of immediate and 24-h cultured islets but abnormal in recipients of 6-day cultured islets. Culture of the islets isolated from human pancreases (cadaveric) resulted in islet purification but at the expense of loss of islets, with only 1--5% surviving 1 wk of culture. During 8--10 days in culture, insulin release declined, and histological examination revealed only a few viable islets. Islets isolated from surgical specimens survived the culture conditions as demonstrated by viable cell clumps and insulin secretion. After an 85% pancreatectomy in the patient with chronic pancreatitis, islets were isolated, cultured for 7 days, and then autografted into muscle pockets and the subcutaneous space of the forearm. There was no evidence of function.
Twenty-four volunteers, mean age 78, including eight mildly non-insulin-dependent diabetics, were randomly allocated to one of two groups and were fed (daily for 8 wk) 9 g of either chromium-rich brewers' yeast (experimental) or chromium-poor torula yeast (control). Before and after yeast supplementation, the serum glucose and insulin response to 100 g oral glucose was measured at 30 min intervals for 2 h. Fasting serum cholesterol, total lipids, and triglycerides were also determined. In the total experimental group (normals + diabetics) and in both the diabetic and nondiabetic experimental subgroups, glucose tolerance improved significantly and insulin output decreased after supplementation. Cholesterol and total lipids fell significantly after supplementation in the total experimental group. The cholesterol decrease was particularly marked in hypercholesterolemic subjects (cholesterol > 300 mg/dl). In the control group, no significant change in glucose tolerance, insulin, triglycerides, or total lipids was found. Cholesterol was significantly lowered in the nondiabetic but not in the diabetic group. Thus, chromium-rich brewers' yeast improved glucose tolerance and total lipids in elderly subjects, while chromium-poor torula yeast did not. An improvement in insulin sensitivity also occurred with brewers' yeast supplementation. This supports the thesis that elderly people may have a low level of chromium and that an effective source for chromium repletion, such as brewers' yeast, may improve their carbohydrate tolerance and total lipids. The improvement in serum cholesterol in some control subjects, as well as in the total experimental group, also suggests the presence of a hypocholesterolemic factor other than chromium in both brewers' and torula yeast.
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The lipolysis, ketosis and hypertriglyceridemia of fasted rats in late pregnancy may be related to decreased insulin secretion geared to decreased glucose availability. In odd-carbon fatty acid enriched (OCE) rats, the odd-carbon fatty acids (OCFA) mobilized during fasting provide terminal three-carbon residues which are glucogenic, thereby permitting blood glucose and insulin to be maintained close to fed levels. The present study has used OCE rats to evaluate the role of insulin in the altered fat metabolism of the fasted rats in late pregnancy. The adipose tissue of 24 female Sprague-Dawley rats was enriched to more than 25% undecanoate (c11:0) and higher OCFA by feeding them a complete diet high in triundecanoin content for six weeks. Twenty-four female controls were fed a similar diet except that the fat was exclusively corn oil. Both OCE and control rats were than mated and on day 18 of pregnancy were divided into four groups: one group was killed fed, one after a 24 h fast, and one after a 48 h fast; the fourth group was fed to day 20 of pregnancy and then killed. In the fed state, the concentrations of glucose, ketones, and cholesterol in serum, as well as that of glycogen in liver, were the same in control and OCE rats. Insulin and triglycerides were similarly elevated in the two groups. After two days of fasting, serum glucose, insulin, and liver glycogen concentrations were significantly higher in OCE than in control rats, while ketones and triglycerides were significantly lower. No significant changes occurred in serum cholesterol. The results are consistent with a predominantly insulin effect in the pregnant OCE rats in diminsihing the marked fasting lipolysis, hyperketonemia and hypertriglyceridemia observed in controls, but do not rule out inhibition of FFA release by in situ re-esterification to glycerol derived from glucose or propionic acid.
1. Sixty-four male rats were fed on a nutritionally complete diet containing 30% of the dietary energy as fat. For thirty-two rats (control) the fat source was maize oil; for the remaining thirty-two rats (experimental) the fat source was triundecanoin-maize oil (7:3, w/w). 2. After 6 weeks, groups of control and experimental rats were fasted and killed on days 0, 1, 2, and 4 of the fasting period. In the experimental group, adipose-tissue fatty acids contained, on average, 246 mmol undecanoic acid/mol total fatty acids. In contrast, the adipose tissue of the control group did not contain odd-carbon-number fatty acids. 3. Plasma glucose levels were significantly higher for all fasted experimental groups and blood ketone levels were significantly lower for these groups. 4. Thus, during prolonged starvation, animals which accumulated odd-C-number fatty acids resisted the development of ketosis. It appeared that odd-C-number fatty acids mobilized from fat depots during fasting may provide their terminal three-C-residues for gluconeogenesis rather than for acetyl-CoA production, thereby allowing for better maintenance of blood glucose and insulin levels than in control animals. 5. It is concluded that the lower acetyl-CoA production and higher blood insulin levels reduce ketogenesis.
Forty-eight male rats were fed a nutritionally complete diet containing 30% of dietary energy as fat. For 24 animals (control) the fat source was corn oil, for the remaining 24 rats (experimental) the fat source was a triundecanoin-corn oil mixture (7:3, wt/wt). After 6 wk, groups of control and experimental rats were killed after 0, 24, and 48 h of fasting. In the experimental group, adipose tissue fatty acids contained, on average, 280 mmol undecanoate/mol fatty acid. In the control group, no odd-numbered fatty acids were present. During fasting, the experimental groups had higher plasma glucose and alanine levels, higher plasma insulin-to-glucagon ration, and lower liver phosphenol pyruvate caboxykinase. The results suggest that the terminal propionate residues generated when odd carbon fatty acids are oxidized become gluconeogenic precursors and cause a reduced need for gluconeogenesis from protein.
The effect of fatty acids on insulin secretion in vitro was investigated. Pieces of pancreas from fed rats were incubated for 15 or 90 min at low (0.6 mg/ml) and high (3.0 mg/ml) glucose concentrations with and without either sodium octanoate or sodium oleate. A highly significant difference in insulin secretion between low and high glucose concentrations indicated viability and responsiveness of the incubated tissue. No statistically significant effect of octanoate or oleate on insulin secretion was found at either low or high glucose concentration. Thus, no support was found for the concept that medium- and long-chain free fatty acids are insulin secretagogues.
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