Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adult Otsuka Long-Evans Tokushima fatty (OLETF) rats lack functional cholecystokinin A (CCK-A) receptors, are diabetic, hyperphagic, and obese, and have patterns of ingestion consistent with a satiety deficit secondary to CCK insensitivity. Because dietary fat potently stimulates CCK release, we examined how dietary fat modulates feeding in adult male OLETF rats and their lean [Long-Evans Tokushima (LETO)] controls. High-fat feeding produced sustained overconsumption of high-fat diet (30% corn oil in powdered chow) over a 3-wk period in OLETF but not LETO rats. We then assessed the ability of gastric gavage (5 ml, 1-2 kcal/ml x 15 s) or duodenal preloads (1 kcal/ml, 0.44 ml/min x 10 min) of liquid carbohydrate (glucose), protein (peptone), or fat (Intralipid) to suppress subsequent 30-min 12.5% glucose intake in both strains. In OLETF rats, gastric and duodenal fat preloads were significantly less effective in suppressing subsequent intake than were equicaloric peptone or glucose. These results demonstrate that OLETF rats fail to compensate for fat calories and suggest that their hyperphagia and obesity may stem from a reduced ability to process nutrient-elicited gastrointestinal satiety signals.
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PMID:Decreased responsiveness to dietary fat in Otsuka Long-Evans Tokushima fatty rats lacking CCK-A receptors. 1051 56

Because of a genetic mutation, the Otsuka-Long-Evans-Tokushima Fatty (OLETF) rat, a model for human non-insulin-dependent diabetes mellitus (NIDDM), shows no expression of the CCK-A receptor gene. We investigated the spontaneous physical activity, sleep, and body temperature in young OLETF rats that had not yet developed diabetes mellitus, and compared these data with age-matched control LETO (non-diabetic strain, Long-Evans-Tokushima-Otsuka) rats. The amount of large movements during the dark phase for the OLETF rats was significantly less than that of control rats. Thus, the amounts of total daily large movement and the ratio of dark-to-light phase movement in the OLETF rats were less than those of control rats, although the amount of small movement was similar for both groups. The diurnal rhythm of body temperature was similar for both groups. In addition, the amount of and circadian rhythm for each vigilance state and slow-wave activity were similar for the two groups. This study demonstrates that the CCK-A receptor might play a role in affecting the level of motor activity, adding hyperphagia, and the circadian rhythm of large movement in these rats prior to the manifestation of NIDDM. In contrast, a CCK-A receptor deficiency does not appear to affect sleep or body temperature in these rats.
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PMID:Spontaneous activity, sleep, and body temperature in rats lacking the CCK-A receptor. 1062 58

Otsuka Long-Evans Tokushima Fatty (OLETF) rats lacking CCK-A receptors are hyperphagic, obese, and diabetic. We have previously demonstrated that these rats have a peripheral satiety deficit resulting in increased meal size. To examine the potential role of hypothalamic pathways in the hyperphagia and obesity of OLETF rats, we compared patterns of hypothalamic neuropeptide Y (NPY), proopiomelanocortin (POMC), and leptin receptor mRNA expression in ad libitum-fed Long-Evans Tokushima (LETO) and OLETF rats and food-restricted OLETF rats that were pair-fed to the intake of LETO controls. Pair feeding OLETF rats prevented their increased body weight and elevated levels of plasma insulin and leptin and normalized their elevated POMC and decreased NPY mRNA expression in the arcuate nucleus. In contrast, NPY expression was upregulated in the dorsomedial hypothalamus (DMH) in pair-fed OLETF rats. A similar DMH NPY overexpression was evident in 5-wk-old preobese OLETF rats. These findings suggest a role for DMH NPY upregulation in the etiology of OLETF hyperphagia and obesity.
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PMID:A role for NPY overexpression in the dorsomedial hypothalamus in hyperphagia and obesity of OLETF rats. 1140 1

Otsuka Long-Evans Tokushima Fatty (OLETF) rat lacking CCK-A receptors are hyperphagic and obese. Previous work has demonstrated alterations in neuropeptide Y (NPY) and proopiomelanocortin (POMC) mRNA expression in ad libitum fed OLETF rats compared to lean Long-Evans Tokushima Otsuka (LETO) controls. In order to determine whether alterations in sensitivity to central peptides involved in overall feeding control may contribute to the hyperphagia and obesity in OLETF rats, we assessed OLETF and LETO rats feeding responses to lateral ventricular infusions of NPY (1 and 3.2 nmol), the melanocortin 3/4 agonist MTII (0.1 and 0.32 nmol) and the melanocortin receptor antagonist SHU-9119 (0.25 and 0.5 nmol). At a 3-h time point, NPY increased food intake in both OLETF and LETO rats. OLETF rats were more sensitive, having significant increases at both NPY doses and a greater increase at the higher dose. The melanocortin agonist MTII decreased intake in both LETO and OLETF rats. At the 20-h time point, the magnitude of suppression was greater in OLETF rats. SHU-9119 increased food intake in both groups. OLETF rats were more sensitive with larger relative increase and longer-lasting effects at the lower dose. These results are consistent with demonstrated alterations in neuropeptide gene expression in OLETF rats and indicate that alterations in responsivity to NPY and melanocortin signaling are unlikely to contribute to their hyperphagia and obesity.
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PMID:Responsivity to NPY and melanocortins in obese OLETF rats lacking CCK-A receptors. 1189 67

Hypothalamic-pituitary-gonadal axis function strongly influences feeding and body weight in cycling females in many species. To test the sufficiency of cyclic variations in plasma estradiol to reproduce normal patterns of spontaneous feeding, food intake, and body weight, ovariectomized Long-Evans rats were subcutaneously injected every fourth day with 2 microg estradiol benzoate or with the oil vehicle alone. Cyclic estradiol treatment completely normalized the trajectory of body weight gain and total food intake through seven treatment cycles. The hyperphagia of ovariectomized rats was expressed as an increase in spontaneous meal size. Meal frequency decreased, but not enough to compensate for the increase in meal size. Estradiol treatment normalized both parameters. In addition, cyclic estradiol treatment produced a further phasic decrease in meal size (and increase in meal frequency) and a decrease in food intake during the second night after injection. This phasic change is similar to the feeding changes occurring during estrus in intact rats. Sexual receptivity was measured during the eighth estradiol treatment cycle, 4 h after injection of 0.5 mg progesterone. Lordosis scores at the time of the treatment cycle modeling estrus were maximal, and scores at the time modeling diestrus were slightly increased over those of rats that did not receive estradiol. Finally, plasma estradiol levels, measured during the ninth treatment cycle, revealed a near-normal cyclic pattern of plasma estradiol levels. These results provide the first demonstration that the induction of a cyclic, near-physiological pattern of plasma estradiol is sufficient to maintain normal levels of body weight, spontaneous feeding patterns, total food intake, and (together with progesterone) sexual receptivity in ovariectomized rats.
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PMID:Cyclic estradiol treatment normalizes body weight and restores physiological patterns of spontaneous feeding and sexual receptivity in ovariectomized rats. 1248 12

Although cholecystokinin A (CCK-A) receptors (CCK-AR) mediate the feeding inhibitory actions of CCK in both rats and mice, the absence of CCK-AR results in species-specific phenotypes. The lack of CCK-AR in Otsuka Long-Evans Tokushima fatty (OLETF) rats results in hyperphagia and obesity. We have suggested that demonstrated increases in meal size and elevated levels of dorsomedial hypothalamic (DMH) neuropeptide Y (NPY) gene expression may contribute to this phenotype. In contrast to OLETF rats, CCK-AR(-/-) mice have normal total daily food intake and do not develop obesity. To assess the basis underlying the different phenotypes in rats and mice lacking CCK-AR, we characterized meal patterns in CCK-AR(-/-) mice and determined whether CCK-AR(-/-) mice exhibited an alteration in DMH NPY gene expression. We demonstrate that although CCK-AR(-/-) mice show a similar dysregulation in meal size as OLETF rats, they do not have an elevation in DMH NPY mRNA expression levels. In fact, intact mice have no CCK-AR in the DMH. Furthermore, in intact rats, NPY and CCK-AR are colocalized in DMH neurons, and parenchymal injection of CCK into the DMH reduces food intake and down-regulates DMH NPY mRNA expression. These results suggest that although CCK-AR plays a role in the mediation of CCK actions in the control of meal size in both rats and mice, CCK-AR seems to contribute to modulating DMH NPY levels only in rats. The deficit in CCK's action in the control of DMH NPY gene expression may play a major role in the obese phenotype in OLETF rats.
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PMID:Differential roles for cholecystokinin a receptors in energy balance in rats and mice. 1512 37

Central administration of neuropeptide Y (NPY) stimulates hyperphagia and hyperinsulinemia. Recent evidence has suggested that the Y1 and Y5 receptor subtypes may both mediate NPY-stimulated feeding. The present study attempts to further characterize the role of central NPY receptor subtypes involved in hyperinsulinemia. NPY and peptide analogs of NPY that selectively activated the NPY Y1 or Y5 receptor subtype induced feeding and hyperinsulinemia in satiated Long Evans rats, whereas NPY analogs that selectively activated the NPY Y2 or Y4 receptor subtype did not. To determine whether NPY-induced hyperinsulinemia is secondary to its hyperphagic effect, we compared the plasma insulin levels in the presence and absence of food after a 1-min central infusion of NPY and its analogs at 15, 60, and 120 min postinfusion. Our data suggest that selective activation of central NPY Y1 receptor subtype induced hyperinsulinemia independent of food ingestion, whereas the NPY Y5 receptor-induced hyperinsulinemia was dependent on food ingestion. Central administration of the selective Y1 receptor agonist D-Arg25 NPY eventually decreased plasma glucose levels 2 h postinfusion in Long Evans rats.
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PMID:Selective activation of central NPY Y1 vs. Y5 receptor elicits hyperinsulinemia via distinct mechanisms. 1518

CCK-A receptor-deficient Otsuka Long-Evans Tokushima fatty (OLETF) rats are hyperphagic and develop obesity and Type 2 diabetes. In this strain, taste preference functions have not been investigated. Therefore, a series of short-access, two-bottle tests were performed in age-matched prediabetic OLETF and nonmutant Long-Evans Tokushima Otsuka (LETO) rats to investigate preference for sucrose (0.03, 0.1, 0.3, or 1.0 M) presented with a choice of water. To discern orosensory from postgastric factors that may contribute to this preference, in a separate experiment, rats were allowed to sham feed sucrose in the absence or presence of duodenal sucrose infusion (0.3, 0.6, or 1.0 M). In the two-bottle real-feeding tests, OLETF rats exhibited a greater preference for 0.3 M sucrose (91.2 +/- 1.7 and 78.5 +/- 3.4% for OLETF and LETO, respectively; P < 0.01) and 1.0 M sucrose (65.3 +/- 1.2 and 57.5 +/- 2.7% for OLETF and LETO, respectively; P < 0.05) than LETO rats. OLETF rats also sham fed less of the lowest (0.03 M; 33.8 +/- 4.8 and 58.3 +/- 7.3 ml for OLETF and LETO, respectively; P < 0.05) and more of the highest (1.0 M; 109.9 +/- 6.5 and 81.0 +/- 3.9 ml for OLETF and LETO, respectively; P < 0.01) concentration of sucrose relative to LETO rats. Finally, intraduodenal sucrose infusions (0.6 and 1.0 M) produced a smaller reduction of 0.3 M sham sucrose intake [14.1 +/- 8.1 vs. 52.5 +/- 3.3 ml and 49.4 +/- 8.0 vs. 82.4 +/- 3.2 ml for 0.6 M (P < 0.01) and 1.0 M (P < 0.05) infusions in OLETF and LETO, respectively]. These findings demonstrate that OLETF rats display an increased preference for sucrose, an effect that is at least partially influenced by the orosensory stimulating effect of sucrose. This enhanced responsiveness to oral stimulation, coupled with the deficit in responding to the postingestive feedback of intestinal sucrose, may contribute additively to the development of hyperphagia and weight gain in OLETF rats.
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PMID:Increased oral and decreased intestinal sensitivity to sucrose in obese, prediabetic CCK-A receptor-deficient OLETF rats. 1535 6

Humans in many countries are currently experiencing what has been called an epidemic of obesity. That is, the average body weight (and amount of fat stored in the body) is increasing over years, carrying with it a multitude of associated medical, psychological, and economic problems. While there is no shortage of possible causes of this epidemic, increased availability and consumption of high-fat (HF), calorically dense and generally quite palatable food is often touted as a likely culprit. In order to better assess the impact of consuming a diet with those qualities, we have developed a well-controlled animal model in which the effects of chronic consumption of a high-fat diet can be dissociated from those of becoming obese per se. Long-Evans rats are fed one of two semipurified pelleted diets, a HF diet that contains 20% fat by weight and a low-fat (LF) diet that contains 4% fat by weight. Pair-fed animals consume the HF diet but are limited to the daily caloric intake of LF rats. Another group receives pelleted chow. Relative to animals consuming diets low in fat, HF animals weigh more, have more carcass fat, are hyperinsulinemic and hyperleptinemic, and are insulin resistant. HF-fed animals, independent of whether they become obese or not, also have central insulin and MTII insensitivity. Finally, HF rats have a down-regulated hypothalamic apo A-IV system that could contribute to their hyperphagia.
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PMID:Consumption of a high-fat diet alters the homeostatic regulation of energy balance. 1562 Oct 62

Mature male Sprague-Dawley (SD) and Long-Evans (LE) rats were instrumented with telemetry transmitters for measurement of heart rate (HR) and housed in room calorimeters for assessment of food intake and oxygen consumption (Vo(2)) at standard laboratory temperatures (23 degrees C) to examine physiological responses to caloric restriction (CR; 60% of baseline ad libitum calories for 2 wk) and refeeding. Ad libitum controls had stable food intake (84-88 kcal/day) and gained weight at rates of 3-4 g/day. Groups from both strains assigned to CR exhibited similar patterns of weight loss and reductions in Vo(2) and HR. Upon refeeding, SD rats exhibited a mild, transient hyperphagic response (1 day) accompanied by sustained suppression of Vo(2) and HR that remained evident 8 days after refeeding. In contrast, LE rats exhibited sustained daily hyperphagia that persisted 8 days after refeeding and was accompanied by a complete restoration of HR and Vo(2). The lower HR and Vo(2) observed during refeeding in SD rats were not due to reduced locomotor activity. The results reveal a strain-dependent divergent response to recovery from CR. We conclude that during recovery from CR, homeostatic stimulation of appetite or suppression of energy expenditure may occur selectively to restore body weight.
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PMID:Long-Evans and Sprague-Dawley rats exhibit divergent responses to refeeding after caloric restriction. 1588 55


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