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

This review summarizes two model systems for understanding how brain neurochemicals, in conjunction with peripheral endocrine and metabolic processes, may be active in controlling very different functions in relation to energy and nutrient balance. As proposed, these systems are unquestionably oversimplified; however, they generate testable hypotheses for future investigations that will help to advance and revise these working models, as well as those of other peptide systems in the brain. Under normal conditions, these peptide systems are behaviorally and endocrinologically specific, and they are activated at very different periods of the daily cycle and at different stages of development. However, under pathologic conditions, their specificity and rhythmicity may be greatly disturbed. This occurs in states involving hypercortisolemia along with hyperinsulinemia or insulin deficiency, when these peptide systems become chronically activated. To determine whether this increased activity actually contributes to conditions of hyperphagia and obesity, and, thus, whether a reversal of this neurochemical activity may help in the treatment of these conditions, critical studies with various pharmacological manipulations are required. Of equal importance are investigations examining the development of these pathologic conditions, from birth to maturity, and their associated disturbances in neurochemical and endocrine processes. A thorough understanding of gene expression in localized brain areas and the contribution of various transcription factors to this process should allow the identification and development of methods that are useful in the treatment, as well as prevention, of disturbed patterns of nutrient intake, fat deposition, and body weight gain.
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PMID:Specificity of hypothalamic peptides in the control of behavioral and physiological processes. 753 Apr 29

1. During the first two thirds of gestation, coinciding with a minimal accretion by the conceptus, the mother is in an anabolic state which is supported by her hyperphagia and the more efficient conservation of exogenous nutrients when she eats. During this phase maternal fat deposits are accumulated thanks to the enhancement in adipose tissue lipogenic and glycerologenic activity. In contrast, in the latter part of gestation, the rapid fetal growth is sustained by the intense transfer of nutrients from maternal circulation. 2. Glucose is quantitatively the most abundant of the several substrates that cross the placenta and despite increased maternal gluconeogenesis this transfer is responsible for the maternal tendency to hypoglycemia. This causes a switch to a net catabolic state which is especially evident in the net breakdown of fat depots. 3. Enhanced release of adipose tissue lipolytic products, free fatty acids (FFA) and glycerol, facilitates the liver synthesis of triglycerides and their later release into circulation associated to very low-density lipoprotein (VLDL). Glycerol is also used as an important gluconeogenic substrate and FFAs are broken down through beta-oxidation for ketone body synthesis. Flow through these pathways becomes increased when food is withheld and this actively contributes to the availability of fuels to the fetus which becomes partially preserved from maternal metabolic insult. Increased liver production of VLDL-triglycerides and decreased extrahepatic lipoprotein lipase contribute to exaggerated maternal hypertriglyceridemia which, besides being a floating metabolic reserve for emergency conditions such as starvation, constitutes an essential substrate for milk synthesis around parturition in preparation for lactation. 4. While the maternal anabolic tendencies found during the first two-thirds of gestation seem to be facilitated by hyperinsulinemia in the presence of a normal responsiveness to the hormone, it is proposed that most of the metabolic changes taking place during the last third of gestation seem to be caused by the insulin-resistant state which is consistently present at this stage, since its reversion caused by sustained exaggerated hyperinsulinemia also reverts several of these metabolic adaptations.
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PMID:Carbohydrate-lipid interactions during gestation and their control by insulin. 754 70

Glutamate-induced obesity of Wistar-rats is known to develop under normophagic and normoinsulinemic conditions, although hyperphagia and hyperinsulinemia are common to obese individuals. Rats of this obesity model show retarded growth, reduced mass of some organs, carcass and whole body as well as an extraordinary high fat content, whereas protein content is reduced. In this study, nitrogen (N) balance, urinary excretion of urea-N, ammonia-N, creatine-N and alpha-amino acid-N and plasma free fatty acid concentration of growing, glutamate-induced obese rats were determined. The main results were independent of frame of reference (mmol N/kg body mass; mmol N/kg0.75 metabolic body mass; N in % of nitrogen intake): Nitrogen intake, urinary excretion of alpha-amino acids and nitrogen excretion in faeces were equal between lean and obese rats. Nitrogen excretion in urine was elevated in obese rats, mainly resulting from increased amounts of urea and ammonia. Nitrogen balance was positive in both groups, but reduced in obese rats. These data point to normal digestion of food proteins, but an unusual high oxidative desamination rate of the absorbed amino acids in obese rats. Taking into account the various hormonal and nerval alterations in glutamate-induced obese rats, resulting e.g. in increased hepatic insulin concentration, the retained amino acid carbon should be channelled into hepatic fatty acid synthesis. Really, unfasted and overnight fasted obese rats showed elevated plasma free fatty acid concentrations. Channeling of amino acids into lipogenesis may explain the low muscle mass and striking fat accumulation--despite normophagia and peripheral normoinsulinemia--of growing, glutamate-induced obese Wistar-rats.
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PMID:Reduced, positive nitrogen balance and elevated plasma free fatty acid concentration in growing, glutamate-induced obese rats. 790 47

The insulin receptor was evaluated at different disease stages in the sand rat (Psammomys obesus), a model for nutrition-induced diabetes. Nondiabetic sand rats showed markedly low receptor number in liver compared with albino rats. Their receptor had an intact tyrosine kinase activity but a higher Km for ATP in the phosphorylation reaction of exogenous substrates. The initial effects of overeating (i.e., development of hyperinsulinemia without hyperglycemia) were associated in the sand rat with a dramatic decrease in in vitro and in vivo insulin-induced receptor tyrosine kinase activity in both liver and muscle. In muscle, this coincided with a decrease in receptor number and an increase in basal tyrosine kinase activity. Similar changes were observed upon development of hyperinsulinemia with hyperglycemia. Upon recovery from the diabetic state by diet restriction, the impaired receptor kinase activation was corrected. Complete restoration occurred only in animals that fully recovered from the diabetic state and became normoinsulinemic. These observations indicate that loss and gain of receptor tyrosine kinase activity were dependent on insulin levels. Thus, overeating may lead to the development of hyperinsulinemia through ineffective extraction of excess insulin by the scarce liver receptors. Hyperinsulinemia, in turn, causes a reversible reduction in receptor kinase activity, leading to insulin resistance. This sequence of events may be relevant to diet-related changes in human non-insulin-dependent diabetes mellitus.
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PMID:Hyperinsulinemia induces a reversible impairment in insulin receptor function leading to diabetes in the sand rat model of non-insulin-dependent diabetes mellitus. 812 94

Given that several genetically obese rodents characterized by hyperphagia, hyperinsulinemia, and insulin resistance have increased hypothalamic neuropeptide Y (NPY) mRNA and peptide content, the impact of NPY administered intracerebroventricularly (i.c.v.) for 7 days to normal, awake rats was investigated. NPY produced marked hyperphagia, increased body weight gain, increased basal insulinemia, and, more importantly, a much greater insulin response to meal feeding than that of saline-infused controls. NPY administration also resulted in a pronounced increase in the in vivo insulin-stimulated glucose uptake by adipose tissue but in a marked decrease in uptake by eight different muscle types. Increased insulin responsiveness of the glucose transport process by adipose tissue was accompanied by increases in both GLUT4 mRNA and protein levels. In contrast, the decreased insulin responsiveness of glucose uptake in muscles from NPY-administered rats was not related to GLUT4 expression. We conclude that i.c.v. NPY administration to normal rats produces a hormonal-metabolic situation that is similar to that reported in the dynamic phase of the genetic obesity of the fa/fa strain. Thus, NPY could be of primary importance in the establishment of obesity syndromes with incipient insulin resistance.
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PMID:Intracerebroventricular administration of neuropeptide Y to normal rats has divergent effects on glucose utilization by adipose tissue and skeletal muscle. 819 61

Ventromedial hypothalamic (VMH) lesion-induced obesity is accompanied by hyperinsulinemia and hyperphagia, which are dependent upon corticosterone (Cort) for their expression. Whether Cort exerts these actions through its stimulation of type I or II Cort receptor populations is unknown. Therefore, food intake and weight gain were measured in obese adrenalectomized VMH-lesioned rats given continuous infusion of various doses of either a type I-receptor agonist (aldosterone), a type II-receptor agonist (RU-28362), or several combination doses. Similarly, the receptor population responsible for lesion-induced hyperinsulinemia was identified. Type II receptor stimulation restored the hyperphagia, weight gain, and hyperinsulinemia of adrenalectomized VMH-lesioned animals, while type I receptor stimulation blocked their weight loss.
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PMID:Relative contribution of type I and II corticosterone receptors in VMH lesion-induced obesity and hyperinsulinemia. 820 42

Microinfusion of bombesin into the lateral ventricles (LV) of rats pretreated with insulin or acutely deprived of food has been demonstrated to reduce core body temperature. Lesions of the ventromedial hypothalamus (VMH) have been shown to produce hyperphagia, hyperinsulinemia, and to alter serum metabolic fuels. The present study examines VMH lesions as a permissive event in bombesin-induced hypothermia in rats tested at normal ambient temperature. A between-group design was used to evaluate the effect of microinjections of bombesin (1, 10, 100 ng) into the LV of rats with bilateral VMH lesions or sham lesions. Core body temperature was recorded over a 240-min period. In animals with lesions of the VMH, hypothermia was demonstrated by 30 min after injection of the 10 ng and 100 ng doses; the hypothermia persisted for 120 min. The 1 ng dose had no effect on body temperature in VMH-lesioned animals. Animals that received sham lesions of the VMH did not demonstrate a reduction in core body temperature at the maximum effective dose (100 ng) of bombesin. These results suggest that some event(s) associated with bilateral VMH lesions acts as a permissive factor in the production of bombesin-induced hypothermia at normal ambient temperature.
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PMID:Bombesin-induced hypothermia in VMH-lesioned rats. 822 Nov 61

The metabolic properties of brown adipose tissue (BAT), liver, and skeletal muscles were compared in lean and obese diabetic SHR/N-cp rats (a new model of type II diabetes) to test whether the severe insulin resistance of obese animals is specifically associated with a thermogenic defect in BAT. The respiratory response of brown adipocytes to norepinephrine and to agents bypassing the adenylate cyclase complex (dibutyryl cyclic AMP and palmitate) was decreased by two-thirds in obese rats, thereby indicating the presence of a major postreceptor defect. Significantly, total BAT cytochrome oxidase activity, uncoupling protein content, and mitochondrial guanosine 5'-diphosphate binding (3 indexes of BAT thermogenic capacity) were also decreased by two-thirds. The specific activities of these parameters expressed per total BAT mitochondrial protein were not altered either. This indicates that the total number of mitochondria per cell is decreased in BAT of obese rats. In contrast, total tissue cytochrome oxidase activity, protein content, and DNA content all increased by two to three times in the liver of obese SHR/N-cp rats, but these parameters remained unchanged in skeletal muscles (vastus lateralis and soleus). Such a remarkable liver hypertrophy may have occurred as a consequence of the persistent hyperphagia-hyperinsulinemia of obese rats that induced a hyperplasia and/or a hepatocyte polyploidization. This observation together with the fact that daily energy expenditure associated with food intake was markedly increased in obese rats (representing as much as 25% of the total energy expenditure) strongly suggests that the liver plays a major role in energy balance in these animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Specific decrease of mitochondrial thermogenic capacity in brown adipose tissue of obese SHR/N-cp rats. 827 28

The effects of ventromedial hypothalamic (VMH) lesions were examined in male and female non-obese non-insulin-dependent diabetic (Goto-Kakizaki [GK]) rats with respect to glucose metabolism and pancreatic insulin content. VMH lesions produced hyperphagia and hyperinsulinemia in both male and female GK rats. In male rats, plasma glucose levels of VMH-lesioned GK rats (22.7 +/- 3.1 mmol/L) were significantly greater than the levels of sham-operated GK rats (10.6 +/- 1.0 mmol/L, P < .001) at 7 weeks after the operation, although there were no differences in these levels between VMH-lesioned and sham-operated groups in Wistar rats. Plasma insulin levels in male VMH-lesioned GK rats tended to be lower at 7 weeks than at 1 week. VMH lesions caused a significant decrease in the pancreatic insulin content of male GK rats (12.0 +/- 2.3 nmol/L/g pancreas) compared with male sham-operated rats (15.8 +/- 1.4 nmol/L/g pancreas, P < .05) 9 weeks postoperatively. In contrast to the results in male rats, female GK rats showed no differences in plasma glucose levels between VMH-lesioned and sham-operated groups at 7 weeks. Female VMH-lesioned GK rats also showed no difference in plasma insulin levels between 1 week and 7 weeks. The pancreatic insulin level of female VMH-lesioned GK rats was unchanged from that of female sham-operated GK rats. The insulin content was significantly greater in the VMH-lesioned Wistar group than in the sham-operated Wistar group, regardless of sex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Marked reduction of pancreatic insulin content in male ventromedial hypothalamic-lesioned spontaneously non-insulin-dependent diabetic (Goto-Kakizaki) rats. 828 72

Medialbasal hypothalamic (MBH) deafferentation induces hypothalamic obesity accompanied by hyperphagia and hyperinsulinemia. Insulin is essential in developing and maintaining obesity, but the role of insulin in food intake in hypothalamic obesity is still unclear. The present study demonstrated that exogenous insulin increased food intake dose relatedly in MBH deafferented diabetic rats without developing hypoglycemia. Insulin administrations suppressed hyperphagia in the sham-operated diabetic rats. In contrast, in the MBH deafferented diabetic rats, insulin increased food intake in sow-related manner concomitant with a greater increased body weight gain than the sham-operated diabetic rats. The blood glucose levels of the MBH deafferented diabetic rats were at all time higher than those of the sham-operated diabetic rats and were hyperglycemic throughout the insulin treatment. These data indicate that insulin action on food intake mediated through the central nervous system is modulated by MBH deafferentation. This modulated insulin action may contribute to the pathogenesis on obesity in MBH deafferented animals.
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PMID:Medialbasal hypothalamic deafferentation modulates feeding response to insulin in rats. 851 Dec 1


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