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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three series of experiments investigated the role of hyperinsulinemia and the vagus nerve in the hyperphagia and obesity syndrome produced in female rats by knife cuts in the ventromedial hypothalamus (VMH). The findings of the first series revealed that VMH cuts do not produce hyperinsulinemia when the rats are prevented from overeating, but insulin levels are elevated in rats allowed to overeat. The second series of experiments demonstrated that VMH-cut rats overconsume sweet sugar solutions during daily short-term tests, and that pharmacological blockade of vagal efferent activity with atropine methyl nitrate fails to inhibit this overconsumption. The third study revealed that subdiaphragmatic vagotomy completely blocks VMH hyperphagia and obesity on a chow diet, but does not prevent overeating and rapid weight gain in rats fed an assortment of highly palatable food. These findings indicate that vagally mediated insulin release is not an essential component to the VMH knife cut syndrome.
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PMID:The role of hyperinsulinema and the vagus nerve in hypothalamic hyperphagia reexamined. 701 36

Parenteral progesterone injections into different mammalian species induce hyperinsulinemia, pancreatic islet hypertrophy, and exaggerated insulin secretion in vitro in response to glucose. The primary effect of progesterone by itself on carbohydrate metabolism appears to be the diversion of glucose utilization away from muscle and fat to other tissues, and the promotion of more storage of glycogen in the liver. On lipid metabolism, the 1 effect of progesterone is to favor storage of depot fat in adipose and breast tissue and to partially reduce the hypertriglyceridemic action of estrogens. On protein metabolism, it has been suggested that progesterone may have a catabolic action in man, and that the basic effects may be a lowering of several plasma amino acids and an increased total urinary nitrogen excretion without an associated aminoaciduria. On ketone body metabolism, progesterone partially suppresses the estrogen effect on liver triglyceride formation while promoting ketogenesis. The metabolic effects of progesterone are most relevant to pregnancy. The hormonal milieu of early to midgestation favors the stimulation of hyperphagia, pancreatic islet hypertrophy, hyperinsulinemia, and body fat and glycogen deposition. This period promotes maternal tissue accretion and weight gain. During the later half of pregnancy, progesterone acts simultaneously with prolactin and other hormones to prepare the breasts for lactation by promoting hyperinsulinemia and fuel storage and by helping to condition the liver in elaborating ketones more promptly to meet the demands of advancing pregnancy.
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PMID:Metabolic effects of progesterone. 703 19

Obese children display constant hyperinsulinism and, frequently, hyperphagia. In animals, lesions of the hypothalamic system affect simultaneously the circadian rhythm of insulin secretion and of food intake. In this study, circadian metabolic rhythm was examined in obese and non-obese children, by two different protocols. (1) Oral glucose tolerance tests (OGTT) were carried out at 9 a.m. and 3 p.m. on 2 consecutive days. (2) Circadian variations of plasma glucose and insulin were determined. After OGTT, in the control children there was a significant drop in the insulin/glucose ratio in the afternoon, whereas in the obese group this ratio remained high, with no significant change during the day. Differences were also observed in free fatty acid, growth hormone, and cortisol responses. The control children showed a circadian rhythm for blood glucose levels which was not present in obesity. These preliminary data suggest impairment of metabolic rhythms in obese children; they should stimulate further studies on the hypothalamic system in obesity.
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PMID:Circadian metabolic rhythms in obese children. 704 63

The effect of two experimental manipulations designed to mobilize lipids from adipose tissue have been investigated in rats with parasagittal knife cuts in the ventromedial hypothalamus (VMH). Those animals which displayed hyperphagia during the initial 5 days VMH knife cuts were then restricted in food intake to reduce body weights to levels comparable to that of the sham-operated controls. Two weeks following the knife-cut lesions, or sham operations, animals in the first experiment were exposed to the cold for 60 min, and those in the second experiment were injected with 2-deoxy-D-glucose (2-DG). The injections of 2-DG increased the level of glycerol in the control animals but not in the animals with VMH knife cuts. Both groups showed a rise in glucose. Plasma insulin and triglycerides were the same in both groups. Exposure to the cold increased the level of glycerol in both groups. The insulin levels were lower in the corresponding groups with knife cuts. These studies show that VMH knife cuts do not produce hyperinsulinemia in pair-gained rats.
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PMID:Obesity-inducing hypothalamic knife cuts: effects on lipolysis and blood insulin levels. 705 66

Weanling male Sprague-Dawley rats received bilateral electrolytic lesions in the ventromedial hypothalamic nuclei (VMNL rats); sham-operated rats served as controls. For 28 post-operative d all animals were fed three equicaloric [16.9 kJ/g (4.03 kcal)] diets with different amounts of macronutrients in each (HCD = high-carbohydrate diet, HFD = high-fat diet and HPD = high-protein diet). VMNL rats selected more than controls from HCD (P less than 0.05) and HFD (P less than 0.01) but similar amounts from the HPD. The total intake from all three diets was greater (P less than 0.001) than that of the controls, but in percent of total diet intakes, VMNL selected proportions comparable to the controls. In terms of macronutient intake, VMNL rats ingested more than controls from each (carbohydrate, P less than 0.001; fat, P less than 0.05; protein, P less than 0.01). Again, in percent of total macronutrient intake, they ingested proportions comparable to the controls. Lee Index (P less than 0.001) was greater and body weight gain/kJ (kcal) smaller (P less than 0.001) in VMNL rats than in controls. However, body weight gains were normal. For the following 14 d, one group of VMNL rats and one control group continued to self-select from the three diets while another VMNL and control group received lab chow [14.2 kJ/g (3.39 kcal)]. Analysis of variance showed a lesion effect for the Lee Index (P less than 0.001) and Lee Index gain /kJ(kcal) (P less than 0.01) but body weight gains and caloric intake were normal among the groups, ie the VMNL rats switched to chow decreased their caloric intake to control levels. On sacrifice, white and brown fat percent protein (P less than 0.001 for both), carcass lipid (P less than 0.001) and protein (P less than 0.01) and plasma insulin (P less than 0.001) showed lesion effects, but there were no differences among the groups in plasma glucose, glycerol, total protein and free-fatty acids. Availability of palatable diets immediately following VMN lesion placement in weanling rats will result in hyperphagia that after one month recedes to normophagia, whether the rats are fed palatable or less palatable diets. Availability of a less palatable diet (chow) following presentation of palatable diets will not result in diminished caloric intake, body weight, obesity and hyperinsulinemia.
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PMID:Hypothalamic obesity in the weanling rat: dietary self-selection, actual macro-nutrient intake, caloric regulation and response to subsequent low palatability diet. 712 49

Several different rodent models are available for metabolic studies on the development of diabetes. Although the abnormalities associated with each diabetes type have many features in common, the documentation of several different genes being involved makes it unlikely that the various syndromes will be reduced to a single disturbance in one metabolic pathway. The severity of the diabetes produced depends on the interaction of the individual mutation with genetic factors in the inbred background of the host. Establishing the nature of these gene-host interactions in rodents should aid us in understanding similar interactions that occur in human diabetes. The development of the syndrome in most models is similar and includes hyperinsulinemia, hyperphagia, and attempts at increasing insulin supply by beta-cell hyperplasia and hypertrophy in the early stages. Hyperglycemia, obesity, and severe diabetes are secondary features that result from a combination of insulin resistance and a failure to sustain the secretion of the large amounts of insulin. Most models utilize ingested food and stored food reserves more efficiently. This increased metabolic efficiency extends to heterozygotes that are normal in all respects having only one dose of the deleterious gene. Establishing this increased metabolic efficiency in heterozygotes lends credence to the thrifty gene hypothesis of diabetes and suggests a mechanism whereby some deleterious diabetes genes may be favored in the human population. The best studied mouse models, and those for which the most complete information is available, are those caused by single genes, e.g., yellow, obese, diabetes, tubby, and fat. In the other models, the mode of inheritance is either polygenic or otherwise unclear, features which interfere with the interpretation of the data. This report briefly summarizes the developing syndrome in each model, points out any differences, and suggests the most appropriate areas where future research should be most productive in the light of contemporary studies.
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PMID:Diabetes-obesity syndromes in mice. 716 May 33

Several different single-gene mutations are known to cause varying degrees of diabetes and obesity in mice. The severity of the diabetes produced depends on both the mutation itself and the interaction of the mutant gene with the inbred background. Establishing the nature of these gene-background interactions should aid us in our understanding of similar interactions that occur in human diabetes. The documentation of several different genes that produce similar, if not identical, diabetes-obesity syndromes suggests that lesions in many pathways can cause diabetes. An understanding of these defects in mice should help us to understand similar defects involved in the human disease. The developmental stages in each mutant are similar. The early symptoms include hyperphagia, hyperinsulinemia, and hypertrophy and hyperplasia of the beta cells of the islets of Langerhans. Hyperglycemia, obesity, and severe diabetes are secondary features that result from insulin resistance and the failure to sustain the secretion of massive amounts of insulin. All models appear to be able to utilize their food in a more efficient manner than normal. Even when restricted to 50% of that amount of food eaten by a normal mouse, mutants are able to maintain their weight and still remain obese. On fasting, the stored fat is utilized more efficiently. One cause of this efficiency in obese and diabetes mice is the ability to convert acetone (the end product of fatty-acid metabolism) to lactate which, in turn, can be converted to glucose, which can sustain continued lipolysis. The occurrence of increased efficiency in obesity and diabetes mutants lends credence to the thrifty-genotype hypothesis regarding the maintenance of the deleterious diabetes genes in human populations.
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PMID:Inherited obesity-diabetes syndromes in the mouse. 724 18

Three areas are identified as important for the genetic influence on the development of obesity, focusing on food intake. (1) Contribution of hyperinsulinemia to the development of hyperphagia and obesity in genetically obese animals. (2) Manipulation of quantity of food intake at various ages in animals. (3) Influence of exercise not only on food intake but on metabolism in the long term.
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PMID:Genetic influence in the development of obesity: focus on food intake. 741 48

Neuropeptide Y (NPY), a major brain neurotransmitter, is expressed in neurons of the hypothalamic arcuate nucleus (ARC) that project mainly to the paraventricular nucleus (PVN), an important site of NPY release. NPY synthesis in the ARC is thought to be regulated by several factors, notably insulin, which may exert an inhibitory action. The effects of NPY injected into the PVN and other sites include hyperphagia, reduced energy expenditure and enhanced weight gain, insulin secretion, and stimulation of corticotropin and corticosterone release. The ARC-PVN projection appears to be overactive in insulin-deficient diabetic rats, and could contribute to the compensatory hyperphagia and reduced energy expenditure, and pituitary dysfunction found in these animals; overactivity of these NPY neurons may be due to reduction of insulin's normal inhibitory effect. The ARC-PVN projection is also stimulated in rat models of obesity +/- non-insulin diabetes, possibly because the hypothalamus is resistant to inhibition by insulin; in these animals, enhanced activity of ARC NPY neurons could cause hyperphagia, reduced energy expenditure, and obesity, and perhaps contribute to hyperinsulinemia and altered pituitary secretion. Overall, these findings suggest that NPY released in the hypothalamuss, especially from the ARC-PVN projection, plays a key role in the hypothalamic regulation of energy balance and metabolism. NPY is also found in the human hypothalamus. Its roles (if any) in human homeostasis and glucoregulation remain enigmatic, but the animal studies have identified it as a potential target for new drugs to treat obesity and perhaps NIDDM.
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PMID:Neuropeptide Y, the hypothalamus, and diabetes: insights into the central control of metabolism. 747 13

We previously reported lower ventromedial hypothalamic nucleus (VMN) serotonergic activity in 11-wk genetically obese vs. lean Zucker rats. To determine whether the activity was secondary to metabolic alterations associated with this established obesity (e.g., significant hyperphagia and hyperinsulinemia), we examined monoaminergic activity in various brain nuclei of 12-day lean (Fa/Fa and Fa/fa) and obese (fa/fa) rats early in the development of obesity. Obese pups had greater percent carcass fat than heterozygotes, both of which were fatter than homozygous lean rats. Obese, but not heterozygous lean, pups were hyperinsulinemic vs. Fa/Fa pups. VMN 5-hydroxy-3-indoleacetic acid levels, an index of serotonin release, were lower in obese and heterozygous than in homozygous lean pups and were not correlated with plasma insulin levels. Although monoamine differences also occurred in several other nuclei, for the most part they appeared to be unrelated to the obese genotype. We conclude that blunted VMN serotonergic activity is not secondary to the obese rat's hyperinsulinemia and may play a significant role in the development of obesity.
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PMID:Serotonergic activity is depressed in the ventromedial hypothalamic nucleus of 12-day-old obese Zucker rats. 752 10


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