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

RhGM-CSF is a hematopoietic growth factor which stimulates the proliferation, differentiation and functional activity of neutrophils, monocytes and macrophages. It also stimulates proliferation of endothelial cells and induces the production of other cytokines, such as interleukin (IL-1), tumor necrosis factor (TNF), interferon, prostaglandin E2, and plasminogen activating factor which affects both hematopoietic and non-hematopoietic cell activities. Initial clinical studies in 1987 generally excluded experimental therapy with rhGM-CSF in pediatric patients (age < or = 17 years) unless life threatening illness related to neutropenia and infection developed (i.e., patients with graft failure). Serious complications of patients undergoing autologous bone marrow transplantation (BMT) related to pancytopenia include infection and hemorrhage. Other regimen related complications include venooclusive disease, pneumonitis and mucositis. As a result of these complications, patients require intensive medical support including antibiotics and hyperalimentation. Initial hospital duration following marrow reinfusion is generally 4 to 5 weeks. Hematopoietic growth factors have been administered to patients undergoing autologous BMT as an attempt to reduce regimen related toxicity.
 ...
PMID:RhGM-CSF in bone marrow transplantation: experience in pediatric patients. 130 85

Studies, such as those on Pima Indians, have shown that metabolic factors are involved in the development of obesity and that being overweight is not simply a result of "sloth and gluttony." However, the environment also affects the development of obesity. Among individuals in a given environment, the variability in body size is influenced by genetically determined responses to that environment. People with a low metabolic rate (adjusted for body size and composition) are prone to weight gain, whereas those with a high level of spontaneous physical activity are less likely to become obese. Similarly, individuals with a high 24-hour respiratory quotient (RQ) are more likely to gain weight than those with a low RQ. Insulin sensitivity (not insulin resistance) is another metabolic predictor of obesity. Genetic linkage studies suggest a number of genes are linked to the development of obesity. By sibling-pair linkage analysis, tumor necrosis factor-alpha (TNF-alpha) was found to be linked to the percentage of body fat, and other studies have shown that fat cell production of TNF-alpha is greater in obese individuals.
 ...
PMID:Metabolic differences and the development of obesity. 767 9

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.
 ...
PMID:Decreased brown fat markedly enhances susceptibility to diet-induced obesity, diabetes, and hyperlipidemia. 853 14

Despite recent advances in antibiotic therapy, aggressive operative intervention and intravenous hyperalimentation, sepsis, and multiple organ failure are still reported to contribute to significant morbidity and mortality in the surgical intensive care unit. In light of this, it is essential to determine the mechanism underlying the pathophysiology of sepsis so that better therapeutic interventions can be designed. Experimental studies indicate that murine polymicrobial sepsis induces a marked suppression in both lymphocytic and macrophage function associated with decreased cellular adenosine triphosphate levels and increased Ca2+. However, such changes are not detectable until approximately 12 h after the onset of sepsis. Alternatively, early (0-4 h) in sepsis, macrophages from the liver and peritoneum exhibit augmented innate secretion of proinflammatory cytokines, tumor necrosis factor, interleukin (IL)-6, and IL-1, associated with the systemic release of these agents. Sustained release of immunosuppressive agents transforming growth factor-beta, IL-4, IL-10, and PGE2, as well as glucocorticoids, are also observed during sepsis. In this regard, many investigators, including us, have suggested that an agent(s) released as a part of this systemic inflammatory response to sepsis may be responsible for the protracted suppression of immune cell function. Studies examining the effects of these mediators in vitro on various immune cells have shown that many of these agents also have the capacity to induce a process referred to as programmed cell death (PCD) or apoptosis (Ao). We have presented evidence of marked changes in the rate of Ao in immune cells after the onset of sepsis. These data suggest the possibility that mediators released in response to septic insult contribute to the observed changes in immune cell function through the induction of Ao. Inasmuch, understanding the contribution of PCD to the pathophysiology of sepsis, should provide a better basis from which to develop more effective therapy for the septic patient.
 ...
PMID:Immune dysfunction in murine polymicrobial sepsis: mediators, macrophages, lymphocytes and apoptosis. 882 95

Uncoupling protein 2 (UCP2) has been proposed to play a prominent role in the regulation of energy balance. UCP2 mRNA expression is upregulated in white adipose tissue (WAT) and liver, but is not altered in skeletal muscle in genetically obese ob/ob mice. The mechanisms involved in the upregulation of UCP2 in obesity have not been investigated. We have now examined the potential role of leptin, hyperphagia, increased tissue lipid content, and overexpression of tumor necrosis factor (TNF)-alpha in the upregulation of UCP2 mRNA expression in the liver and WAT in ob/ob mice. Treatment of ob/ob mice with leptin for 3 days significantly reduced their food intake but had no effect on the upregulation of UCP2 mRNA levels in the liver or WAT. To investigate the effect of feeding and higher tissue lipid content on the upregulation of UCP2 in liver and WAT, we compared UCP2 mRNA levels in ad-libitum fed and 72-h fasted control and ob/ob mice. In controls, fasting had no effect on UCP2 mRNA levels in liver, but increased UCP2 mRNA in WAT suggesting that the effects of fasting on UCP2 mRNA levels are tissue-specific. In ob/ob mice, fasting did not lower UCP2 mRNA levels in liver or WAT suggesting that the upregulation of UCP2 in ob/ob mice is not merely a direct consequence of increased food intake. 72-h fasting lowered hepatic total lipid content by 34% and 36% in control and ob/ob mice, respectively, without any corresponding decrease in hepatic UCP2 mRNA levels, suggesting that the enhanced UCP2 expression in the liver of ob/ob mice is not secondary to lipid accumulation in their livers. Although TNF-alpha has been shown to acutely increase UCP2 mRNA levels in liver and WAT, and is overexpressed in adipose tissue in obesity, deletion of the genes for both TNF receptors in ob/ob mice produces a further increase in UCP2 mRNA expression in liver and adipose tissue indicating a paradoxical inhibitory role. Taken together, these results suggest that the upregulation of UCP2 mRNA levels in the liver and WAT of ob/ob mice is not due to the lack of leptin, hyperphagia, increased tissue lipid content, or over-expression of TNF-alpha.
 ...
PMID:Upregulation of uncoupling protein 2 mRNA in genetic obesity: lack of an essential role for leptin, hyperphagia, increased tissue lipid content, and TNF-alpha. 1068 29

Data from both rodent models and humans suggest that intact neuronal melanocortin signaling is essential to prevent obesity, as mutations that decrease the melanocortin signal within the brain induce hyperphagia and excess body fat accumulation. Melanocortins are also involved in the pathogenesis of disorders at the opposite end of the spectrum of energy homeostasis, the anorexia and weight loss associated with inflammatory and neoplastic disease processes. Studies using melanocortin antagonists (SHU9119 or agouti-related peptide) or genetic approaches (melanocortin-4 receptor null mice) suggest that intact melanocortin tone is required for anorexia and weight loss induced by injected lipopolysaccharide (an inflammatory gram-negative bacterial cell wall product) or by implantation of prostate or lung cancer cells. Although the precise mechanism whereby peripheral inflammatory/neoplastic factors activate the melanocortin system remains unknown, the proinflammatory cytokines (interleukin-1, interleukin-6, and tumor necrosis factor-alpha) that are produced in the hypothalamus of rodents during both inflammatory and neoplastic disease processes likely play a role. The data presented in this paper summarize findings that implicate neuronal melanocortin signaling in inflammatory anorexia.
 ...
PMID:Melanocortin signaling and anorexia in chronic disease states. 1285 26

The study population in this report by Lin et al. was ob/ob mice that have an inherited genetic deficiency of the appetite-suppressing hormone leptin. These mice develop hyperinsulinemia, insulin resistance, and fatty livers. Compared with their lean littermates and wild-type C57BL-6 mice, ob/ob mice have hepatomegaly. In this study, the authors compared three different groups of adult mice (aged 8-10 wk), including male ob/ob C57BL-6 mice, their lean littermates, and wild-type C57BL-6 mice of the same age and sex. The primary purpose of this study was to test the efficacy of metformin for treatment of fatty liver disease in obese, ob/ob mice that develop hyperinsulinemia or insulin resistance and fatty livers. Metformin therapy was found to eliminate fatty liver disease in this model. The potential mechanisms of the action of metformin were the inhibition of hepatic tumor necrosis factor (TNF)alpha and several TNF-inducible responses, which are likely to promote hepatic steatosis and necrosis. In these experiments, ob/ob mice were divided into three treatment groups. Group 1 consisted of eight mice that were treated with metformin and permitted to consume a nutritiously replete liquid mouse diet ad libitum. Mice in group 2 (n = 8) did not receive metformin but were pair-fed the same volume of liquid diet that the mice in the metformin-treated group had consumed on the previous day. Obese ob/ob mice in group 3 (n = 4) and lean mice received no metformin, as with the mice in group 2, but were permitted to consume the liquid diet ad libitum. Liquid diet was given to facilitate accurate daily comparison of food intake among the various treatment groups. All mice were weighed at the beginning of the study and weekly thereafter until killed and then sera, fat, and liver tissues were collected. Tissues were either fixed in buffered formalin and processed from the deceased mice for histology or snap frozen in liquid nitrogen and stored until RNA and proteins were isolated. The feeding protocol was repeated with a second group of 18 ob/ob mice. After 4 wk, hepatocytes were obtained by in situ liver perfusion with collagenase and assayed for cellular adenosine triphosphate (ATP) content. In each experiment, hepatocytes isolated from 3 mice from each treatment group were suspended in a medium and pooled for subsequent analysis to evaluate cell viability, determine the number of obtained cells, and to assay cellular ATP content. These experiments were repeated using another 3 mice from each treatment group, so that analysis of hepatocytes took place from six ob/ob mice in each feeding group.Hepatic steatosis was decreased significantly only in the metformin-treated group. The authors found that metformin's beneficial effect on the fatty liver disease of mice was not due to its ability to constrain hyperphagia, nor due to decreased caloric ingestion, because the daily caloric intakes of the metformin-treated mice and the pair-fed control mice were virtually identical. These caloric intakes were consistently approximately 20% less than that of another obese control group that was permitted to consume diet ad libitum. The authors also observed no significant effect of metformin on serum glucose concentration from fed, ob/ob mice. Metformin is known to reduce hyperinsulinemia by about 40% in both of these obese hyperinsulinemic and insulin-resistant rodent strains. In conclusion, Lin et al. documented that metformin improves fatty liver disease and reverses hepatomegaly, steatosis, and aminotransferase abnormalities in mice. In addition, the authors suggest that metformin might inhibit dieting-induced redistribution of lipid from the liver to adipose tissue depots. In summary, this study identifies a potential treatment for fatty liver disease in humans.
 ...
PMID:Current biochemical studies of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis suggest a new therapeutic approach. 1449 93

Wasting can occur at an early stage of HIV infection. Both reduced energy intake and increased resting energy expenditure (REE) have been considered as factors in wasting with predominant lean body mass loss, suggesting disturbances of protein metabolism. Our aim was to study protein-energy metabolism in relation to body composition and oral energy intake in asymptomatic patients with HIV infection but receiving no active antiretroviral therapy. Stable-weight asymptomatic male patients (n = 8) at stage A of HIV infection with a detectable viral load were compared with 9 healthy control men. Protein metabolism was studied in the postabsorptive state using a primed constant infusion of l-[1-(13)C]leucine and l-[2-(15)N]glutamine. REE was studied by indirect calorimetry, body composition by bioelectrical impedance, and energy intake by dietary records. BMI and lean body mass did not differ between patients and controls. In HIV-infected subjects, energy intake, protein breakdown, protein synthesis, and REE were 57% (P < 0.05), 18% (P < 0.05), 22% (P < 0.05) and 14% (P < 0.05) greater than in controls, respectively. REE and protein breakdown were correlated (r = 0.73, P < 0.05). The hormonal profile was normal in HIV-infected subjects with the exception of low urinary C-peptide and plasma reverse triiodothyronine. Plasma interleukin-6 and tumor necrosis factor-alpha were greater than in controls, but energy intake was 1.53 times the REE in the HIV-infected men. Thus, at the asymptomatic stage of HIV infection, increased protein turnover contributes to the increase in the REE. Moderate hyperphagia, which occurred despite increased levels of cytokines, in conjunction with increased protein synthesis maintains a normal body composition, without significant loss of lean body mass.
 ...
PMID:Hyperphagia contributes to the normal body composition and protein-energy balance in HIV-infected asymptomatic men. 1533 20

The various mechanisms that may explain the association between brain dysfunction and the pathogenesis of metabolic syndrome (MS) leading to cardiovascular disease and type 2 diabetes have been reviewed. A Medline search was conducted until September 2003, and articles published in various national and international journals were reviewed. Experts working in the field were also consulted. Compelling evidence was found that saturated and total fat and low dietary n-3 fatty acids and other long-chain polyunsaturated fatty acids (PUFAs) in conjunction with sedentary behavior and mental stress combined with various personality traits can enhance sympathetic activity and increase the secretion of catecholamine, cortisol and serotonin, all of which appear to be underlying mechanisms involved in MS. Excess secretion of these neurotransmitters in conjunction with underlying long-chain PUFA deficiency may damage the neurons in the ventromedial hypothalamus and insulin receptors in the brain, in particular during fetal life, infancy and childhood, and lead to their dysfunction. Since 30-50% of the fatty acids in the brain are long-chain PUFAs, especially omega-3 fatty acids which are incorporated in the cell membrane phospholipids, it is possible that their supplementation may have a protective effect. Omega-3 fatty acids are also known to enhance parasympathetic activity and to increase the secretion of anti-inflammatory cytokines as well as acetylecholine in the hippocampus. It is possible that a marginal deficiency of long-chain PUFAs, especially n-3 fatty acids, due to poor dietary intake during the critical period of brain growth and development in the fetus, and later in the infant and also possibly in the child, adolescent and adult may enhance the release of tumor necrosis factor-alpha (TNF-alpha) interleukin (IL)-1, 2 and 6 and cause neuronal dysfunction. Experimental studies indicate that ventromedial hypothalamic lesions in rats induce hyperphagia, resulting in glucose intolerance and insulin resistance. Treatment with neuropeptide Y abolished hyperphagia and ob mRNA (leptin mRNA) in this animal model. Long-term infusion of norepinephrine and serotonin into the ventromedial hypothalamus impaired pancreatic islet function inasmuch as ventromedial hypothalamic norepinephrine and serotonin levels were elevated in hyperinsulinemic and insulin-resistant animals. Treatment with insulin was associated with restoration of hypothalamic neurotransmitter abnormalities, indicating that ventromedial hypothalamus dysfunction can impair pancreatic beta cells resulting in metabolic abnormalities consistent with MS. Treatment with omega-3 fatty acids, beta blockers, ACE inhibitors, estrogen, and meditation may have a beneficial effect on insulin receptors and ventromedial hypothalamic dysfunction. However, no definite or precise insight into the pathophysiological link between MS, brain function and nutrition is available. Despite this, epidemiological studies and intervention trials indicate that treatment with n-3 fatty acids may be adopted in clinical practice and used to direct therapy for prevention of type 2 diabetes, hypertension, coronary artery disease (CAD), and atherosclerosis, thereby indicating that MS may also respond to this treatment.
 ...
PMID:Can brain dysfunction be a predisposing factor for metabolic syndrome? 1575 41

It is proposed that metabolic syndrome X is initiated in the perinatal period as a low-grade systemic inflammatory condition. Increased consumption of energy-dense diets by pregnant women and lactating mothers suppresses the activities of Delta-6 and Delta-5 desaturases not only in maternal tissues but also in fetal liver and the placenta, resulting in decreased plasma and tissue concentrations of long-chain polyunsaturated fatty acids omega-6 arachidonic acid (AA), omega-3 eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). EPA, DHA, and AA have negative feedback control on tumor necrosis factor-alpha and IL-6 synthesis. Hence, EPA, DHA, and AA deficiencies induced by an energy-dense diet increase generation of tumor necrosis factor-alpha and interleukin-6, markers of inflammation that in turn decrease production of endothelial nitric oxide and adiponectin to induce insulin resistance in maternal and fetal tissues. Increased concentrations of tumor necrosis factor-alpha and interleukin-6 enhance expression and activity of 11beta-hydroxysteroid dehydrogenase type 1 enzyme, which produces abdominal obesity, insulin resistance, hyperlipidemia, hyperphagia, and hyperleptinemia, characteristic features of metabolic syndrome X. Continued consumption of an energy-dense diet in childhood aggravates these molecular events. This implies that supplementation of long-chain polyunsaturated fatty acids (especially AA, EPA, and DHA in appropriate ratios) from the perinatal period through adulthood could prevent, arrest, or postpone development of metabolic syndrome X.
 ...
PMID:Pathophysiology of metabolic syndrome X and its links to the perinatal period. 1592 3


1 2 Next >>