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)

Ethanol toxicity on liver is a function of duration of alcoholism, amount of daily intake of alcohol and patient's nutrition. The threshold of alcohol toxicity on the liver is about 40 g of ethanol daily in men and 20-30 g in women, however liver cirrhosis develops in no more than 8-20% of patients exceeding this values. Ethanol is oxidized in the liver to acetaldehyde--a compound considerably more toxic than ethanol itself. Despite small amount of alcohol dehydrogenase (ADH) found in gastric mucosa, the metabolism of ethanol in this site may have an important hepatoprotective effect. The oxidation of ethanol is associated with a change of hepatocyte redox homeostasis, which leads to a number of metabolic disorders such as lactic acidosis, hyperlipidaemia and hyperuricaemia. Chronic ethanol consumption does not influence ADH activity, but has a profound stimulatory effect on microsomal enzymes, in particular cytochrome CYP2E1. This fact is responsible for development in alcoholic liver associated with rise of oxygen consumption, excessive production of free radicals and increased metabolism of ethanol, vitamin A and testosterone. Ethanol and acetaldehyde have a deleterious effect, both the direct and indirect, on hepatocytes e.g., generating radical oxygen species and damaging intestinal mucosal barrier. Cellular oxidative stress that is caused by both an excess of free radicals and the antioxidatives' deficiency (glutathion, vitamin E, phosphatidylcholine), may be the principal factor responsible for progression of alcoholic liver disease. Among other factors accelerating alcohol-related liver lesion there are certain drugs, high fat diet, infection with HCV and genetic factors (female sex, enzymatic polymorphic forms of ADH and ALDH, hemochromatosis). Great importance in pathogenesis of necrotic and inflammatory hepatic events is being attributed to portal endotoxaemia and cytokines induced within the liver, in particular TNF-alpha and interleukin 8. These cytokines play a key role in development of alcoholic hepatitis, which clinical severity ranges from subclinical to fatal forms. Apart from abstinence, the treatment of alcohol liver disease is based on hyperalimentation, since alcoholism is generally associated with protein malnutrition. In severe forms of alcohol hepatitis corticosteroids are recommended.
 ...
PMID:[Alcoholic liver disease]. 1290 Dec 71

A byproduct of the aging of the population has been a dramatic rise in patients with dementia. The aim of the present study is to clarify the use of aggressive and palliative treatments, artificial nutrition and sedation in long-term care hospitals in Japan. We assessed 123 deaths in people aged 65 and older who died in two long-term care hospitals in and around Nagoya from January 2001 to December 2002. All deceased were divided into two groups according to their diagnosis of dementia. Data on the particular characteristics of the deceased, diagnosis of dementia, aggressive treatments (including CPR, intubation, mechanical ventilation, the use of systemic antibiotics and blood transfusion), palliative treatments (including oxygen, narcotic and nonnarcotic pain medication) artificial nutrition (including hyperalimentation and tube feeding) and sedation during the last six months of their lives were collected from medical charts. The prevalence of aggressive and palliative interventions did not vary significantly with the diagnosis of dementia except for the use of vasopressors. Artificial nutrition was prevalent and few patients received sedatives in either group. Patients with and without dementia received similar treatments in the end-stage. A greater understanding of the course of dementia is needed to further discussions on the terminal care of people with dementia. A national consensus on how to treat end-stage demented patients is also needed.
 ...
PMID:[Terminal care for elderly patients with dementia in two long-term care hospitals]. 1499 24

Inactivating mutations of the pro-opiomelanocortin (POMC) gene in both mice and humans leads to hyperphagia and obesity. To further examine the mechanisms whereby POMC-deficiency leads to disordered energy homeostasis, we have generated mice lacking all POMC-derived peptides. Consistent with a previously reported model, Pomc(-/-) mice were obese and hyperphagic. They also showed reduced resting oxygen consumption associated with lowered serum levels of thyroxine. Hypothalami from Pomc(-/-) mice showed markedly increased expression of melanin-concentrating hormone mRNA in the lateral hypothalamus, but expression of neuropeptide Y mRNA in the arcuate nucleus was not altered. Provision of a 45% fat diet increased energy intake and body weight in both Pomc(-/-) and Pomc(+/-) mice. The effects of leptin on food intake and body weight were blunted in obese Pomc(-/-) mice whereas nonobese Pomc(-/-) mice were sensitive to leptin. Surprisingly, we found that Pomc(-/-) mice maintained their acute anorectic response to peptide-YY(3-36) (PYY(3-36)). However, 7 days of PYY(3-36) administration had no effect on cumulative food intake or body weight in wild-type or Pomc(-/-) mice. Thus, POMC peptides seem to be necessary for the normal response of energy balance to high-fat feeding, but not for the acute anorectic effect of PYY(3-36) or full effects of leptin on feeding. The finding that the loss of only one copy of the Pomc gene is sufficient to render mice susceptible to the effects of high fat feeding emphasizes the potential importance of this locus as a site for gene-environment interactions predisposing to obesity.
 ...
PMID:Mice lacking pro-opiomelanocortin are sensitive to high-fat feeding but respond normally to the acute anorectic effects of peptide-YY(3-36). 1507 Jul 80

To address whether defective melanocortin activation is one element of leptin resistance with age, we infused centrally the melanocortin agonist, MTII and antagonist, SHU9119 in young and old rats. Food intake, energy expenditure, adiposity, BAT UCP1, and leptin expression in white fat as well as hypothalamic expressions of MC3R, MC4R, POMC, AgRP and NPY were assessed. The MTII-evoked anorexia was transient whereas the SHU9119-induced hyperphagia was sustained in young and old. MTII elevated oxygen consumption in both ages. The oxygen consumption waned gradually in young but increased continuously in aged following MTII infusion. The MTII-mediated induction in BAT UCP1 was similarly robust in both ages as was the SHU9119-mediated suppression in UCP1. POMC and MC3/4 receptor expressions were unaltered with age. These findings demonstrate the effectiveness of MTII to bypass leptin resistance in aged-obese rats. The equally strong orexigenic response to SHU9119 coupled with unaltered POMC expression and food intake in the young versus old suggest that melanocortin tone is unchanged with age despite impaired melanocortin activation by leptin.
 ...
PMID:Aged-obese rats exhibit robust responses to a melanocortin agonist and antagonist despite leptin resistance. 1546 33

To investigate mechanisms of resistance to obesity, the physiologic responses to short-term moderate fat feeding were studied at ambient temperature (T(a)) = 23 degrees C and thermonuetrality (T(a) = 30 degrees C) in mice susceptible (B6) or resistant (A/J) to obesity. We hypothesized that A/J mice would exhibit greater adaptive thermogenic responses to consumption of moderate-fat diets, and that this response would be attenuated in thermoneutral conditions due to reduced activity of brown adipose tissue (BAT). B6 and A/J mice were adapted to either T(a) = 23 degrees C or T(a) = 30 degrees C, implanted with telemetry devices, housed in metabolic chambers for measurement of food intake, oxygen consumption (Vo(2)), and heart rate (HR), and studied before and during 1 week of consuming a diet containing 32% of calories from fat. Access to 32% fat diet resulted in increased caloric intake in both strains, but caloric intake for A/J mice returned to baseline levels within 72 hours, while B6 mice remained hyperphagic. Both strains exhibited increased light-phase Vo(2) indicative of adaptive thermogenesis; however, there was no strain difference in light-phase Vo(2) during the 1-week feeding trial. Surprisingly, T(a) had no effect on diet-induced thermogenesis in either mouse strain. Moderate high-fat feeding produced mild tachycardia that was similar in B6 and A/J mice and more clearly evident at thermonuetrality. We conclude that adaptive thermogenic responses are intact in both mouse strains studied at thermoneutrality, suggesting a minimal role for BAT in the initial metabolic response to hyperphagia. Furthermore, the results suggest that differences in control of caloric intake, rather than capacity for adaptive thermogenesis, may contribute to the relative susceptibility to obesity in A/J and B6 mice.
 ...
PMID:Adaptive thermogenesis is intact in B6 and A/J mice studied at thermoneutrality. 1553 95

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.
 ...
PMID:Long-Evans and Sprague-Dawley rats exhibit divergent responses to refeeding after caloric restriction. 1588 55

A cluster of unique pathologies progressively develops during chronic total- or rapid eye movement-sleep deprivation (REM-SD) of rats. Two prominent and readily observed symptoms are hyperphagia and decline in body weight. For body weight to be lost despite a severalfold increase in food consumption suggests that SD elevates metabolism as the subject enters a state of negative energy balance. To test the hypothesis that mediation of this hypermetabolism involves increased gene expression of uncoupling protein-1 (UCP1), which dissipates the thermodynamic energy of the mitochondrial proton-motive force as heat instead of ATP formation in brown adipose tissue (BAT), we 1) established the time course and magnitude of change in metabolism by measuring oxygen consumption, 2) estimated change in UCP1 gene expression in BAT by RT-PCR and Western blot, and 3) assayed serum leptin because of its role in regulating energy balance and food intake. REM-SD of male Sprague-Dawley rats was enforced for 20 days with the platform (flowerpot) method, wherein muscle atonia during REM sleep causes contact with surrounding water and awakens it. By day 20, rats more than doubled food consumption while losing approximately 11% of body weight; metabolism rose to 166% of baseline with substantial increases in UCP1 mRNA and immunoreactive UCP1 over controls; serum leptin decreased and remained suppressed. The decline in leptin is consistent with the hyperphagic response, and we conclude that one of the mediators of elevated metabolism during prolonged REM-SD is increased gene expression of UCP1 in BAT.
 ...
PMID:Chronic REM-sleep deprivation of rats elevates metabolic rate and increases UCP1 gene expression in brown adipose tissue. 1572 48

Mitochondrial uncoupling protein-1 (UCP1) has been thought to be a key molecule for thermogenesis during cold exposure and spontaneous hyperphagia and thereby in the autonomic regulation of energy expenditure and adiposity. However, UCP1 knockout (KO) mice were reported to be cold intolerant but unexpectedly did not get obese even after hyperphagia, implying that UCP1 may not be involved in the regulation of adiposity. Treatment of obese animals with beta3-adrenergic agonists is known to increase lipid mobilization, induce UCP1, and, finally, reduce body fat content. To obtain direct evidence for the role of UCP1 in the anti-obesity effect of beta3-adrenergic stimulation, in the present study, UCP1-KO and wild-type (WT) mice were fed on cafeteria diets for 8 wk and then given a beta3-adrenergic agonist, CL-316,243 (CL), or saline for 2 wk. A single injection of CL increased whole body oxygen consumption and brown fat temperature in WT mice but not in KO mice, and it elicited almost the same plasma free fatty acid response in WT and KO mice. WT and KO mice increased similarly their body and white fat pad weights on cafeteria diets compared with those on laboratory chow. Daily treatment with CL resulted in a marked reduction of white fat pad weight and the size of adipocytes in WT mice, but not in KO mice. Compared with WT mice, KO mice expressed increased levels of UCP2 in brown fat but decreased levels in white fat and comparable levels of UCP3. It was concluded that the anti-obesity effect of beta3-adrenergic stimulation is largely attributable to UCP1, but less to UCP2 and UCP3, and thereby to UCP1-dependent degradation of fatty acids released from white adipose tissue.
 ...
PMID:Indispensable role of mitochondrial UCP1 for antiobesity effect of beta3-adrenergic stimulation. 1636 88

Null mutations of the proopiomelanocortin gene (Pomc) cause obesity in humans and rodents, but the contributions of central versus pituitary POMC deficiency are not fully established. To elucidate these roles, we introduced a POMC transgene (Tg) that selectively restored peripheral melanocortin and corticosterone secretion in Pomc mice. Rather than improving energy balance, the genetic replacement of pituitary POMC in PomcTg mice aggravated their metabolic syndrome with increased caloric intake and feed efficiency, reduced oxygen consumption, increased subcutaneous, visceral, and hepatic fat, and severe insulin resistance. Pair-feeding of PomcTg mice to the daily intake of lean controls normalized their rate of weight gain but did not abolish obesity, indicating that hyperphagia is a major but not sole determinant of the phenotype. Replacement of corticosterone in the drinking water of Pomc mice recapitulated the hyperphagia, excess weight gain and fat accumulation, and hyperleptinemia characteristic of genetically rescued PomcTg mice. These data demonstrate that CNS POMC peptides play a critical role in energy homeostasis that is not substituted by peripheral POMC. Restoration of pituitary POMC expression to create a de facto neuronal POMC deficiency exacerbated the development of obesity, largely via glucocorticoid modulation of appetite, metabolism, and energy partitioning.
 ...
PMID:Glucocorticoids exacerbate obesity and insulin resistance in neuron-specific proopiomelanocortin-deficient mice. 1644 60

Casitas b-lineage lymphoma (c-Cbl) is a multiadaptor protein with E3-ubiquitin ligase activity involved in regulating the degradation of receptor tyrosine kinases. We have recently reported that c-Cbl(-/-) mice exhibit a lean phenotype and enhanced peripheral insulin action likely due to elevated energy expenditure. In the study reported here, we examined the effect of a high-fat diet on energy homeostasis and glucose metabolism in these animals. When c-Cbl(-/-) mice were fed a high-fat diet for 4 weeks, they maintained hyperphagia, higher whole-body oxygen consumption (27%), and greater activity (threefold) compared with wild-type animals fed the same diet. In addition, the activity of several enzymes involved in mitochondrial fat oxidation and the phosphorylation of acetyl CoA carboxylase was significantly increased in muscle of high-fat-fed c-Cbl-deficient mice, indicating a greater capacity for fat oxidation in these animals. As a result of these differences, fat-fed c-Cbl(-/-) mice were 30% leaner than wild-type animals and were protected against high-fat diet-induced insulin resistance. These studies are consistent with a role for c-Cbl in regulating nutrient partitioning in skeletal muscle and emphasize the potential of c-Cbl as a therapeutic target in the treatment of obesity and type 2 diabetes.
 ...
PMID:Casitas b-lineage lymphoma-deficient mice are protected against high-fat diet-induced obesity and insulin resistance. 1650 34


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>