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)

Previous studies have indicated that rodents are relatively resistant to diet-induced obesity and that this resistance may be mediated in part by the capacity for diet-induced thermogenesis in brown adipose tissue (BAT). To test this hypothesis, we fed UCP-DTA transgenic with toxigene-mediated ablation of BAT and their control littermates a "Western diet" [21% (wt/wt) fat] or normal mouse chow [6.5% (wt/wt) fat]. The diets were begun at weaning (19 days old). At the age of 12 weeks, transgenic mice receiving the Western diet were markedly obese. The increased body weight and total body lipid content were significantly greater in transgenic mice receiving the Western diet than were the additive individual effects of Western diet (in control mice) and decreased BAT (in chow-fed mice), suggesting a synergistic interaction between diminished BAT and diet. A synergistic effect of Western diet and BAT ablation was also observed for morbid metabolic complications, such as insulin resistance, hyperglycemia, and hyperlipidemia. These metabolic changes were accompanied by increased expression of tumor necrosis factor-alpha and decreased expression of GLUT4 and beta 3-adrenergic receptor messenger RNA levels in white adipose tissue of UCP-DTA transgenic mice receiving the Western diet compared to those in the other experimental groups. As previously described, transgenic mice with diminished brown fat are hyperphagic. Of note, the degree of hyperphagia in transgenics compared to controls was similar whether the animals were fed chow or a Western diet. Thus, the synergistic effect of Western diet on obesity in transgenic mice was not mediated by a further stimulation of food intake. Overall, this study demonstrates the existence of a synergistic interaction between decreased BAT and Western diet to cause marked obesity and its accompanying disorders, such as insulin resistance and hyperlipidemia, and gives further support for the view that an important function of BAT is protection from diet-induced obesity, diabetes, and insulin resistance.
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PMID:Decreased brown fat markedly enhances susceptibility to diet-induced obesity, diabetes, and hyperlipidemia. 853 14

The high prevalence of obesity and its well documented association with the cardiovascular risk factors diabetes mellitus, dyslipidemia and hypertension represents a major problem for the general health status of industrialized societies. Although numerous studies have shown that genetic factors have a major influence on the regulation of energy homeostasis and the susceptibility to obesity, the genes and predisposing mutations involved are insufficiently understood. Among several known rodent models of obesity due to single gene mutations, mice homozygous for the obese (ob) gene exhibit massive early-onset obesity, hyperphagia, non-insulin-dependent diabetes mellitus, defective thermoregulation and infertility. Recently the ob gene was identified by positional cloning and shown to be mutated in ob/ob mice. Leptin, the product of the ob gene, is a 167-amino acid secreted protein that is synthesized exclusively in adipose tissue. With the exception of ob/ob mice, circulating plasma leptin is elevated in obesity. Administration of recombinant leptin to ob/ob mice reduces fat mass, food intake, hyperglycemia and hyperinsulinemia. The various effects of the hormone are mediated by leptin receptors expressed at high levels in the hypothalamus, but also in several other non-neuronal tissues. A mutation in the leptin receptor gene is responsible for the obese phenotype of db/db mice. Plasma leptin in humans is positively correlated with body fat mass, suggesting that leptin resistance rather than leptin deficiency is a common feature of human obesity. This review briefly summarizes the current status of the rapidly growing evidence that leptin plays an important role in the regulation of body weight and fat deposition.
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PMID:Regulation of energy balance by leptin. 888 45

Genetically obese (ob/ob) mice display a number of metabolic alterations, including decreased thermogenesis, hyperphagia, hyperglycemia and increased body fat. A single intracerebroventricular (i.c.v.) injection of these mice with leptin (0.01 to 1 microg) lowered food intake and body weight within 24 h. In addition, i.c.v. administration of leptin increased 22 h energy expenditure while reducing the respiratory quotient (RQ) in a dose-dependent manner. The leptin-induced decrease in RQ suggests a reduction in the fraction of total energy derived from carbohydrate oxidation and a corresponding increase in energy derived from fat oxidation. Our data suggest that leptin controls energy homeostasis through activation of receptor(s) in the central nervous system (CNS) that regulate both food intake and energy metabolism.
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PMID:Intracerebroventricular injection of leptin increases thermogenesis and mobilizes fat metabolism in ob/ob mice. 901 37

It is generally thought that typical atherosclerotic lesions do not develop in the rodent. The Goto-Kakizaki (GK) rat is a nonobese strain in which a spontaneous type of non-insulin-dependent diabetes mellitus develops without apparent macroangiopathy. In our previous study, making ventromedial hypothalamic (VMH) lesions in GK rats induced hyperphagia and a further deterioration in glucose metabolism. In the current study, male GK rats in which VMH lesions were made were examined for vascular changes, with special reference to atherosclerotic lesions. Marked hyperglycemia in GK rats with VMH lesions (hereafter referred to as VMH lesion rats) was revealed over an observation period (plasma glucose levels 16 weeks after the operation: VMH lesion GK rats, 19.3 +/- 2.0 mmol/L, vs sham-operated GK rats, 10.1 +/- 1.3 mmol/L; p < 0.0001). Light microscopic observation of the descending aorta in VMH lesion GK rats 16 weeks after the surgery revealed that the intimal thickening and the number of infiltrating cells into the intima were significantly increased as compared with sham-operated GK rats (17531 +/- 3747 microm2 vs 3072 +/- 1192 microm2, p < 0.0001; 15.6 +/- 3.1 per one transverse section vs 6.8 +/- 2.5 per one transverse section, p < 0.0005). Electron microscopic observations demonstrated an increased number of microvilli and lysosomes in endothelial cells, infiltration of macrophages and lymphocytes into the intima, and migration of medial smooth muscle cells into the intima that are considered to be early events in atherosclerosis. These morphologic changes could be induced by a deterioration in glucose metabolism. This rat may thus be useful for studying the process of the initiation of atherosclerosis in diabetes mellitus.
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PMID:Early morphologic changes of atherosclerosis induced by ventromedial hypothalamic lesion in the spontaneously diabetic Goto-Kakizaki rat. 901 56

The melanocortin-4 receptor (MC4-R) is a G protein-coupled, seven-transmembrane receptor expressed in the brain. Inactivation of this receptor by gene targeting results in mice that develop a maturity onset obesity syndrome associated with hyperphagia, hyperinsulinemia, and hyperglycemia. This syndrome recapitulates several of the characteristic features of the agouti obesity syndrome, which results from ectopic expression of agouti protein, a pigmentation factor normally expressed in the skin. Our data identify a novel signaling pathway in the mouse for body weight regulation and support a model in which the primary mechanism by which agouti induces obesity is chronic antagonism of the MC4-R.
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PMID:Targeted disruption of the melanocortin-4 receptor results in obesity in mice. 901 99

The present study was undertaken to study the effects of chronic treatment with lisinopril on the cardiovascular complications in streptozotocin (STZ) diabetic and deoxycorticosteroneacetate (DOCA) hypertensive rats. Injection of STZ produced severe glycosuria (> 2%), hyperglycemia, hypoinsulnaemia, polydypsia, polyphagia and loss of body weight. It also produced hypothyroidism, hypercholesterolaemia, hypertriglyceridaemia, hypertension, bradycardia and decreased left ventricular developed pressure (LVDP). Elevation in serum creatinine level and increased activity of liver enzymes were also found in STZ treated animals. DOCA by itself did not produce any change in blood glucose but reduced serum insulin levels in non-diabetic animals. However, in the diabetic group, DOCA reduced blood sugar levels. Treatment of STZ-diabetic rats with DOCA did not aggravate cardiac depression or hyperglycaemia. Treatment of rats with lisinopril (1 mg kg-1, p.o. daily for six weeks), in diabetic and diabetic hypertensive animals prevented STZ induced loss of body weight and hypertension, bradycardia and hypothyroidism. It also prevented STZ induced hyperglycemia and hypoinsulinaemia in both diabetic and diabetic hypertensive animals. There was a reduction in cholesterol, triglyceride, and LDL levels; the ratio between total cholesterol to HDL and LDL to HDL and an improvement in LVDP at higher filling pressure in diabetic as well as diabetic hypertensive animals. Treatment with lisinopril also prevented hypertrophy and elevated levels of serum creatinine, SGOT and SGPT in diabetic animals. In conclusion, the present data suggests that STZ-DOCA model may not be considered as the ideal model for the study of cardiovascular complications of combined treatment hypertension and diabetes. However, the present investigation presents a number of beneficial effects of lisinopril treatment in diabetic with or without hypertensive rats and it may be considered as one of the drugs of choice in treatment of hypertension when it is associated with diabetes mellitus.
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PMID:Effects of chronic treatment with lisinopril on cardiovascular complications in streptozotocin diabetic and DOCA hypertensive rats. 907 44

The case of a woman of 27 affected by the Prader-Willi syndrome who underwent general anaesthesia for dental surgery is reported. The patient presented severe mental retardation, small stature, moderate muscular hypotonia, hyperphagia, obesity, and diabetes mellitus. Premedication consisted of diazepam and atropine; anaesthesia was induced with propofol and maintained with propofol, fentanyl and N2O; muscle paralysis was obtained with atracurium. A small glottis was observed at laryngoscopy so that a 6 mm cuffed tube was inserted. Surgery lasted 75 minutes; the patient recovered promptly a few minutes following the end of propofol infusion; no postoperative complication was recorded. As hypoglycemia can occur during and after surgery in the Prader-Willi syndrome, plasma samples for glucose, NEFA, insulin, cortisol, and growth hormone (GH) were collected prior to the induction of anaesthesia (A), 20 minutes after starting surgery (B), at the end of surgery (C), and 3 hours later (D). In spite of the infusion of glucose, hyperglycemia was observed just in C and D samples (A:77; B:88; C:245; D:279 mg/dl). Stable NEFA values, within the normal range, were observed (A:77; B:88; C:245; D:279 mg/dl) suggesting poor or absent lipolysis. Insulin decreased progressively during surgery (A:10.5; B:8.8; C:5.4; D:7.0 mU/L). Cortisol peaked in B (A:9.5; B:20.9; C:13.4; D:4.8 micrograms/dl), suggesting normal hypothalamic reactivity to the surgical stimulus. Finally very low GH levels were observed (A:0.04; B:0.07; C:0.06; D:0.09 ng/ml) suggesting GH deficiency, which had possibly affected the size of patient's glottis. Our data support the hypothesis that hypoglycemia in the Prader-Willi syndrome originates from inadequate lipolysis during starvation.
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PMID:[General anesthesia in Prader-Willi syndrome]. 910 80

Food intake was restricted to 75% of ad libitum levels in 37 male Psammomys obesus (Israeli Sand Rats) from the ages of 4 (weaning) to 10 weeks. Energy restriction reduced the mean bodyweight at 10 weeks by 29% compared with 44 ad libitum fed controls. Hyperglycemia was prevented completely in the food-restricted group, and mean blood glucose concentrations were significantly reduced (3.8 +/- 0.2 vs. 5.5 +/- 0.4 mumol/L; p < 0.05) compared with control animals. Plasma insulin concentrations were also decreased significantly compared with ad libitum fed controls (105 +/- 13 vs. 241 +/- 29 mU/L; p < 0.05). Although energy restriction prevented hyperglycemia from developing in 10-week-old P. obesus, 19% of the food restricted animals still developed hyperinsulinemia. We concluded that hyperphagia between the ages of 4 to 10 weeks may be essential for the development of noninsulin-dependent diabetes mellitus in P. obesus, but that hyperinsulinemia may still occur in the absence of hyperphagia and hyperglycemia, suggesting a significant genetic influence on the development of hyperinsulinemia in this animal model.
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PMID:The effect of dietary energy restriction on body weight gain and the development of noninsulin-dependent diabetes mellitus (NIDDM) in Psammomys obesus. 919 93

Herein we present the case of a 12-year-old boy who attended our clinic for obesity and hyperphagia. As a newborn he was noted to have diffuse muscular hypotonia and poor sucking response. At the age of 11 years, he was admitted to hospital for respiratory insufficiency. He had personality disorders characterized by temper tantrums and violent outbursts including self-mutilation. Physical evaluation revealed marked central obesity, he had small hands and feet, and also genital hypoplasia. Of the biochemical parameters, hyperglycemia and a low serum testosterone level must be emphasized. The patient fulfills the clinical criteria of typical Prader-Willi syndrome. Cytogenetic and fluorescence in situ hybridization analysis showed a karyotype 47,XXY, del(15)(q11;q13). To our knowledge this is the first report of the aforementioned genotype expressed as Prader-Willi phenotype in childhood.
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PMID:A case with 47,XXY,del(15)(q11;q13) karyotype associated with Prader-Willi phenotype. 919 10

New Zealand Obese (NZO) mice exhibit a polygenic syndrome of hyperphagia, obesity, hyperinsulinemia, and hyperglycemia similar to that observed in young diabetes mutant mice on the C57BLKS/J background (C57BLKS/J-Lepr(db)/Lepr(db)). Here we show that in NZO this syndrome is accompanied by a marked elevation of the leptin protein in adipose tissue and serum. The promoter region and the complementary DNA of the ob gene of NZO mice, including its 5'-untranslated region, are identical with the wild-type sequence (C57BL, BALB/c), except that the transcription start is located 5 bp upstream of the reported site. In contrast to C57BLKS/J+/+ and C57BL/6J-Lep(ob)/Lep(ob) mice, NZO mice failed to respond to recombinant leptin (7.2 microg/g) with a reduction of food intake. Leptin receptor messenger RNA as detected by PCR appears as abundant in hypothalamic tissue of NZO mice as in tissue from lean mice. Ten nucleotide polymorphisms are found in the complementary DNA of the leptin receptor, resulting in two conservative substitutions (V541I and V651I) in the extracellular part of the receptor and one nonconservative substitution (T1044I) in the intracellular domain between the presumed Jak and STAT binding boxes. However, these mutations are also present in the related lean New Zealand Black strain (body fat at 9 weeks: New Zealand Black, 6.2 +/- 1.3%; NZO, 17.0 +/- 1.7%). Thus, the polymorphic leptin receptor seems to play only a minor, if any, role in the obesity and hyperleptinemia of the NZO mouse. It is suggested that the main defect in NZO is located distal from the leptin receptor or at the level of leptin transport into the central nervous system.
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PMID:Hyperleptinemia, leptin resistance, and polymorphic leptin receptor in the New Zealand obese mouse. 932 35


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