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

Several metabolic parameters were used to determine the evolution of the diabetic state of streptozotocin diabetic rats treated with aqueous leaf extracts from Myricia uniflora, a plant widely used in northern Brazil for treatment of diabetes. The effect of the extracts on the intestinal absorption of glucose and on the evolution of diabetes of diabetic rats adapted to a high protein, carbohydrate-free diet were also investigated. Treated rats received twice a day, by gavage, during three weeks, 7.5 mg of lyophilized powder, corresponding to about 60 mg of dried leaves, prepared from percolations with boiled water, Treatment of diabetic rats fed a stock, balanced diet did not affect body weight gain but reduced the hyperglycemia, polyphagia, polydipsia, urine volume and the urinary excretion of glucose and urea. Myrcia administration for 3 weeks had no effect on the weight of epididymal and retroperitoneal adipose tissue, or on the concentrations of pancreatic and serum insulin. The intestinal absorption of glucose, measured with a perfusion technique in situ, was markedly inhibited by Myrcia (7.5 mg of lyophilized powder per ml of perfusion solution). The effects of Myrcia treatment on diabetic rats adapted to a carbohydrate-free diet were similar to those obtained in rats fed the stock diet. The data show that aqueous extracts of Myrcia has a beneficial effect on the diabetic state, mainly by improving metabolic parameters of glucose homeostasis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Assessment of the antidiabetic activity of Myrcia uniflora extracts in streptozotocin diabetic rats. 820 37

Mutation of the obese (ob) gene results in severe hereditary obesity and diabetes in the C57BL/6J and related strains of mice. In this study we examined the expression of the ob gene in a dietary model in which moderate obesity develops in response to fat (58% of calories from fat) without mutation of the ob gene, and in four genetic models of obesity in mice: ob/ob, db/db, tubby, and fat. Several white and brown adipose depots were examined (epididymal, subcutaneous, perirenal, and interscapular). Northern blot analysis shows that levels of ob mRNA are increased in all adipose depots examined in every model of obesity. The average fold increases were 12.0 +/ 2.1 (ob/ob), 4.8 +/- 1.5 (db/db), 2.8 +/- 0.1 (tubby), 2.4 +/- 0.3 (fat), and 2.1 +/- 0.2 (high fat diet-induced A/J). Moreover, we found that the expression of the ob gene could be manipulated by pharmacologically blocking the development of diet-induced obesity. Supplementation of a high fat diet with a beta 3-adrenergic receptor agonist (CL316,243) prevented obesity, but not hyperphagia associated with high fat feeding (body weights of high fat-fed A/J mice = 34.0 +/- 1.0 g; high fat plus CL316,243-fed mice = 26.8 +/- 0.5 g; n = 10). CL316,243-treated, high fat-fed animals contained levels of ob mRNA in all adipose depots that were equal to or less than levels in low fat-fed mice (average levels in high fat plus CL316,243-fed mice relative to low fat-fed mice: 0.93 +/- 0.09). Inasmuch as fat cell size, but not number, was increased in a previous study in diet-induced obese A/J mice, these results indicate that expression of the ob gene serves as a sensor of fat cell hypertrophy, independent of any effects on food intake.
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PMID:Pharmacologic manipulation of ob expression in a dietary model of obesity. 862 12

Leptin acts on the brain to inhibit feeding, increase thermogenesis, and decrease body weight. Neuropeptide Y (NPY)-ergic neurons of the hypothalamic arcuate nucleus (ARC) that project to the paraventricular nuclei (PVN) and dorsomedial nuclei (DMH) are postulated to control energy balance by stimulating feeding and inhibiting thermogenesis, especially under conditions of energy deficit. We investigated whether leptin's short-term effects on energy balance are mediated by inhibition of the NPY neurons. Recombinant murine leptin (11 microg) injected into the lateral ventricle of fasted adult Wistar rats inhibited food intake by 20-25% between 2 and 6 h after administration, compared with saline-treated controls (P < 0.05). Uncoupling protein mRNA levels in brown adipose tissue (BAT) rose by 70% (P < 0.01). Leptin treatment significantly reduced NPY concentrations by 20-50% (P < 0.05) in the ARC, PVN, and DMH and significantly decreased hypothalamic NPY mRNA levels (0.61 +/- 0.02 vs. 0.78 +/- 0.03 arbitrary units; P < 0.01). A second study examined changes in leptin during 5 days' intracerebroventricular NPY administration (10 microg/day), which induced sustained hyperphagia and excessive weight gain. In NPY-treated rats, leptin mRNA levels in epididymal fat were comparable to those in saline-treated controls (0.94 +/- 0.17 vs. 1.0 +/- 0.28 arbitrary units; P > 0.1), but plasma leptin levels were significantly higher (4.88 +/- 0.66 vs. 2.85 +/- 0.20 ng/ml; P < 0.01). Leptin therefore acts centrally to decrease NPY synthesis and NPY levels in the ARC-PVN projection; reduced NPY release in the PVN may mediate leptin's hypophagic and thermogenic actions. Conversely, NPY-induced obesity results in raised circulating leptin concentrations. Leptin and the NPY-ergic ARC-PVN neurons may interact in a homeostatic loop to regulate body fat mass and energy balance.
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PMID:Interactions between leptin and hypothalamic neuropeptide Y neurons in the control of food intake and energy homeostasis in the rat. 903 86

Hyperphagia and obesity can be experimentally induced in rodents by microinjection of 6-hydroxydopamine (6-OHDA) into the ventral noradrenergic bundle (VNAB) to interrupt efferent catecholaminergic pathways to the hypothalamus. Since hypothalamic neuropeptide Y (NPY) is implicated in the control of ingestive behavior, we evaluated hypothalamic NPY activity in this model of obesity. Adult male rats injected bilaterally with 12 microg of 6-OHDA in the VNAB displayed an enhanced rate of body weight gain and selective dark-phase hyperphagia that started at about 10 days postinjection and persisted for the entire duration of the experiment. NPY gene expression, assessed by ribonuclease protection assay, was significantly higher in the hypothalami of 6-OHDA-treated hyperphagic rats during the dark phase (p < 0.01 vs. levels during the light phase and in control, vehicle-injected rats). We also evaluated gene expression of NPY Y and Y5 receptors, receptor subtypes reported to mediate NPY-induced feeding. The dark-phase increase in NPY mRNA was accompanied by the concomitant upregulation of NPY Y5R gene expression, but not of Y1R mRNA levels. Leptin, the peripheral hormone secreted by adipocytes, is believed to maintain body weight and inhibit food intake, most likely by suppressing hypothalamic NPY activity. Evaluation of leptin gene expression in the epididymal fat revealed that the upregulation of leptin mRNA noted during the dark phase in control rats did not occur in 6-OHDA-treated rats. These observations implied that the normal restraint on NPY and feeding exercised by leptin in control rats may be abrogated in 6-OHDA-treated hyperphagic rats due to insufficient levels of leptin. If so, administration of leptin should inhibit food intake in these rats. Indeed, injection of leptin (2 mg/kg, intraperitoneally (i.p.)) on 2 consecutive days reduced 24-h food intake by 25% and significantly reduced body weight. These results suggest that the nocturnal hyperphagia and resultant obesity induced by 6-OHDA injected into the VNAB may be attributed to leptin deficiency concomitant with increased hypothalamic NPY.
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PMID:Evidence that dark-phase hyperphagia induced by neurotoxin 6-hydroxydopamine may be due to decreased leptin and increased neuropeptide Y signaling. 961 6

Elevated levels of serum free fatty acids (FFA) may be the metabolic alteration in obesity that leads to insulin resistance (IR) and type 2 diabetes mellitus (DM). The obese Zucker rat (ZR) is a genetic model of juvenile-onset obesity and type 2 DM. Compared with its lean sibling, the obese ZR is hyperinsulinemic, hypertriglyceridemic, and, beginning at about 6 months, hyperglycemic. The obese ZR demonstrates also IR, hyperphagia, increased lipogenesis, adipocyte hypertrophy and hyperplasia, and increased serum FFA levels. This study was designed to determine if serum FFA levels in lean and obese ZRs correlate with metabolic parameters associated with altered energy metabolism and IR. We hypothesized that serum FFA levels correlate with such serum parameters such as insulin, glucose, triglyceride, and total cholesterol, as well as such tissue parameters as retroperitoneal, perirenal, and epididymal fat pad weights and liver total lipid content. Twenty lean and 20 obese ZR were age/weight matched. For 14 days each rat had ad libitum access to a single bowl diet that was 50% fat, 30% carbohydrate, and 20% protein. Body weights and caloric intakes were measured daily. After 14 days, all animals were fasted overnight and euthanized. Serum and tissue measurements were made and various parameters were correlated with FFA levels. Serum FFA levels were almost 2 times higher in the obese ZR (approximately 1 mmol/L) compared to the lean (approximately 0.6 mmol/L). Each variable measured was significantly (p < or = 0.05) greater in the obese ZR compared to the lean. There were significant correlations between serum FFA levels and certain variables when data from all ZR were plotted against serum and tissue parameters. However, within phenotypes, there were no significant correlations. Serum FFA levels predict serum and tissue parameters that accompany obesity and IR when comparing lean and obese rats. However, FFA do not predict such parameters within one phenotype.
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PMID:Can associations between free fatty acid levels and metabolic parameters determine insulin resistance development in obese Zucker rats? 1171 70

Some, but not all, fats are obesogenic. The aim of the present studies was to investigate the effects of changing type and amount of dietary fats on energy balance, fat deposition, leptin, and leptin-related neural peptides: leptin receptor, neuropeptide Y (NPY), agouti-related peptide (AgRP), and proopiomelanocortin (POMC), in C57Bl/6J mice. One week of feeding with a highly saturated fat diet resulted in ~50 and 20% reduction in hypothalamic arcuate NPY and AgRP mRNA levels, respectively, compared with a low-fat or an n-3 or n-6 polyunsaturated high-fat (PUFA) diet without change in energy intake, fat mass, plasma leptin levels, and leptin receptor or POMC mRNA. Similar neuropeptide results were seen at 7 wk, but by then epididymal fat mass and plasma leptin levels were significantly elevated in the saturated fat group compared with low-fat controls. In contrast, fat and leptin levels were reduced in the n-3 PUFA group compared with all other groups. At 7 wk, changing the saturated fat group to n-3 PUFA for 4 wk completely reversed the hyperleptinemia and increased adiposity and neuropeptide changes induced by saturated fat. Changing to a low-fat diet was much less effective. In summary, a highly saturated fat diet induces obesity without hyperphagia. A regulatory reduction in NPY and AgRP mRNA levels is unable to effectively counteract this obesogenic drive. Equally high fat diets emphasizing PUFAs may even protect against obesity.
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PMID:Effects of dietary fat types on body fatness, leptin, and ARC leptin receptor, NPY, and AgRP mRNA expression. 1200 66

We investigated if agouti-related peptide (AgRP), an endogenous antagonist of melanocortin receptors (MC3-R and MC4-R), effects energy expenditure in rats. Fragments of the carboxyl-terminal, AgRP (83-132), and the amino-terminals, AgRP (25-51) and AgRP (54-82), were administered intracerebroventricularly (ICV). Food intake, body weight and fat weight changes were measured 5 and/or 24 h after a single ICV injection of the fragments. Oxygen consumption and colonic temperature were measured as indices of energy expenditure, during 3 and 24 h after the ICV injections, respectively. An oral glucose tolerance test was performed 24 h after ICV AgRP (83-132) injection. Binding experiments were performed in HEK-293 cells that over-expressed human MC4-R. AgRP (83-132), but not AgRP (25-51) nor AgRP (54-82), induced a potent and long-lasting increase in the cumulative food intake. Both the carboxyl-terminal and amino-terminal AgRP fragments significantly decreased oxygen consumption and colonic temperature. Despite the absence of hyperphagia and cross-reactivities with MC4-R, AgRP (25-51) and AgRP (54-82) significantly increased body weight and epididymal/mesenteric fat weight. AgRP (83-132) did not affect glucose and insulin responses to the oral glucose tolerance test. AgRP causes a potent and long-lasting decrease in energy expenditure; an effect that is exhibited by carboxyl-terminal fragments and amino-terminal fragments that lack antagonist activity at the MC receptors. This suggests that the amino-terminal region of AgRP plays a regulatory role in energy metabolism.
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PMID:Acute intracerebroventricular administration of either carboxyl-terminal or amino-terminal fragments of agouti-related peptide produces a long-term decrease in energy expenditure in rats. 1288 55

To investigate the relationship between development of obesity and the small intestinal functions two experimental models of male Wistar rats were used in the present work: 1) early postnatally overfed rats, nursed from birth to weaning in small litters (SL, 4 pups/nest), and 2) neonatally monosodium glutamate treated rats (MSG 2 mg/g b.w. administered s.c. for 4 days after birth) submitted to the same early nutritional manipulation. After weaning, all animals had free access to a standard pellet diet and at 40 and 80 days of age their body weight, body fat content and food consumption as well as changes of the brush-border-bound duodenal and jejunal alkaline phosphatase (AP) activity were compared with parameters of the offsprings raised under normal feeding conditions (NL, 8 pups/nest). At 40 and 80 days of age the postnatally overfed pups from SL nests became heavier, displayed a significantly increased epididymal plus retroperitoneal fat pad weight (P<0.01) and significantly higher AP activity in both segments of the small intestine (P<0.01) in comparison with rats nursed in NL nests, although their mean daily food intake did not differ from that of non-obese rats during the postweaning periods examined. In contrast, the same treatment of MSG rats had only a small effect on late appearance of obesity, i.e. in early postnatally overfed and normally fed MSG rats a similar pattern of body weight, food intake, adiposity and AP activity was found after weaning. The effect of MSG-treatment was also accompanied by the appearance of normophagia, hypophagia and stunted growth on day 40 and day 80, respectively. Moreover, the size of fat depots and the increase of brush-border-bound AP activity in MSG rats belonging to the SL and NL groups was quantitatively similar to the values size of these parameters observed in SL obese rats subjected to early postnatal overnutrition. These results indicate that postnatal nutritional experience (overnutrition) may represent a predisposing factor in control rats from small litters for the development of obesity in later life. Permanently increased small intestinal AP activity observed after weaning in both models of obesity when hyperphagia is not present suggest that these functional changes and associated alterations in food digestion could be a component of regulatory mechanisms contributing to the maintenance of their elevated body fat weight.
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PMID:Obesity and changes of alkaline phosphatase activity in the small intestine of 40- and 80-day-old rats subjected to early postnatal overfeeding or monosodium glutamate. 1504 54

The blood concentration of agouti-related protein (AgRP), a protein related to hyperphagia and obesity, is increased in obese human and fasted lean subjects. Because there is no saturable transport system at the blood-brain barrier for circulating AgRP to reach its central nervous system target, uptake of AgRP by peripheral organs might be physiologically meaningful. Using the biologically active fragment AgRP(82-131), we determined the pharmacokinetics of its radioactively labeled tracer after iv bolus injection and compared it with that of the vascular marker albumin. AgRP enters peripheral organs at different influx rates, all of which were higher than into brain and spinal cord. At 10 min after iv injection, the radioactivity recovered in the liver, which had the fastest influx rate for AgRP, represented intact (125)I-AgRP. The adrenal gland had a moderately fast uptake (but the highest initial volume of distribution), followed by the heart, lungs, and skeletal muscle. By comparison, epididymal fat, testis, and pancreas had low permeability to AgRP. Saturation of influx was determined by coadministration of excess unlabeled AgRP and was shown to be present in the liver and adrenal gland. The influx rate and initial volume of distribution did not show a linear correlation with vascular permeability or regional blood flow. AgRP uptake by the liver and epididymal fat was significantly increased by overnight fasting, whereas that by the adrenal gland was significantly decreased in fasted mice. Thus, the differential uptake of AgRP by peripheral organs could be a regulated process that is modulated by food deprivation.
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PMID:Selective tissue uptake of agouti-related protein(82-131) and its modulation by fasting. 1614 94

The use of experimental models of diabetes mellitus (DM) has been useful in understanding the complex pathogenesis of DM. Streptozotocin (STZ) injected in rats during the neonatal period has usually led to the major features described in diabetic patients (hyperglycemia, polyphagia, polydipsia, polyuria, and abnormal glucose tolerance) in a short period. Diabetes mellitus is a product of low insulin sensibility and pancreatic beta-cell dysfunction. Its process is characterized by a symptomless prediabetic phase before the development of the disease. In this study, we investigated the long-term effects of diabetes induction regarding the cellular metabolic aspects of this model and its similarities with diabetes found in humans. Male Wistar rats (5-day old) were intraperitoneally injected with STZ (150 mg/kg) and followed up for 12 weeks. On the 12th week, animals were decapitated and peri-epididymal fat pads were excised for adipocyte isolation. The following studies were performed: insulin-stimulated 2-deoxy-d-[(3)H]glucose uptake; incorporation of d-[U-(14)C]-glucose into lipids and conversion into (14)CO(2); and insulin binding. The weight gain rate of the STZ-treated group became significantly lower by the eighth week. These rats developed polyphagia, polydipsia, polyuria, and glycosuria, and impaired glucose tolerance. Biological tests with isolated adipocytes revealed a reduction in the insulin receptor number and an impairment in their ability to oxidize glucose as well as to incorporate it into lipids. Interestingly, parallel to reduced body weight, the adipocyte size of STZ rats was significantly small. We concluded that apart of a decrease in pancreatic insulin content, this experimental model of DM promotes a remarkable and sustained picture of insulin resistance in adulthood that is strongly related to a loss in adipose mass.
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PMID:Neonatal streptozotocin-induced diabetes mellitus: a model of insulin resistance associated with loss of adipose mass. 1757 Feb 61


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