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)

The incidence of obesity, with its associated health risks, is on the increase throughout the western world affecting all age groups, including children. The typical western diet is high in fat and sugar and low in complex carbohydrates. This study looks at the effects of feeding an equivalent high-energy (HE) diet to growing rats. Juvenile male Sprague-Dawley rats that were fed an HE (18.9 kJ/g) diet starting approximately 10 d after weaning gained less weight than littermates fed a nonpurified (14 kJ/g) diet. Despite an initial hyperphagia following the change in diet, HE rats also consumed less energy. Although they exhibited reduced weight gain, HE rats were relatively obese; fat pad weights were elevated for all 4 dissected depots. HE-fed rats exhibited symptoms of developing metabolic syndrome with elevated plasma concentrations of glucose, triglycerides, nonesterified fatty acids, insulin, and leptin. In addition, leptin receptor gene expression in the hypothalamic arcuate nucleus (ARC) and ventromedial nucleus of HE rats was reduced. Consistent with the elevated serum leptin and other peripheral signals in HE rats, hypothalamic gene expression for the orexigenic neuropeptides, neuropeptide Y (ARC and dorsomedial nucleus), and agouti-related peptide (AgRP), was reduced. This reduction in orexigenic signaling and decline in energy intake is consistent with an apparent attempt to counter the further development of an obese state in rats consuming an energy-dense diet. The juvenile Sprague-Dawley rat has potential in the development of a model of childhood diet-induced obesity.
 ...
PMID:Hypothalamic gene expression is altered in underweight but obese juvenile male Sprague-Dawley rats fed a high-energy diet. 1517 98

Neuropeptide Y is the most potent physiological appetite transducer known. The NPY network is the conductor of the hypothalamic appetite regulating orchestra in the arcuate nucleus-paraventricular nucleus (ARC-PVN) of the hypothalamus. NPY and cohorts, AgrP, GABA and adrenergic transmitters, initiate appetitive drive directly through Y1, Y5, GABAA and alpha1 receptors, co-expressed in the magnocellular PVN (mPVN) and ARC neurons and by simultaneously repressing anorexigenic melanocortin signaling in the ARC-PVN axis. The circadian and ultradian rhythmicities in NPY secretion imprint the daily circadian and episodic feeding patterns. Although a number of afferent hormonal signals from the periphery can directly modulate NPYergic signaling, the reciprocal circadian and ultradian rhythmicities of anorexigenic leptin from adipocytes and orexigenic ghrelin from stomach, encode a corresponding pattern of NPY discharge for daily meal patterning. Subtle and progressive derangements produced by environmental and genetic factors in this exquisitely intricate temporal relationship between the two opposing humoral signals and the NPY network promote hyperphagia and abnormal rate of weight gain culminating in obesity and attendant metabolic disorders. Newer insights at cellular and molecular levels demonstrate that a breakdown of the integrated circuit due both to high and low abundance of NPY at target sites, underlies hyperphagia and increased adiposity. Consequently, interruption of NPYergic signaling at a single locus with NPY receptor antagonists may not be the most efficacious therapy to suppress hyperphagia and obesity. Central leptin gene therapy in rodents has been shown to subjugate, i.e. bring under homeostatic control, NPYergic signaling and suppress the age-related and dietary obesity for extended periods and thus shows promise as a newer treatment modality to curb the pandemic of obesity and metabolic syndrome.
 ...
PMID:NPY and cohorts in regulating appetite, obesity and metabolic syndrome: beneficial effects of gene therapy. 1533 72

For examining whether dissipating excess energy in the liver is a possible therapeutic approach to high-fat diet-induced metabolic disorders, uncoupling protein-1 (UCP1) was expressed in murine liver using adenoviral vectors in mice with high-fat diet-induced diabetes and obesity, and in standard diet-fed lean mice. Once diabetes with obesity developed, hepatic UCP1 expression increased energy expenditure, decreased body weight, and reduced fat in the liver and adipose tissues, resulting in markedly improved insulin resistance and, thus, diabetes and dyslipidemia. Decreased expressions of enzymes for lipid synthesis and glucose production and activation of AMP-activated kinase in the liver seem to contribute to these improvements. Hepatic UCP1 expression also reversed high-fat diet-induced hyperphagia and hypothalamic leptin resistance, as well as insulin resistance in muscle. In contrast, intriguingly, in standard diet-fed lean mice, hepatic UCP1 expression did not significantly affect energy expenditure or hepatic ATP contents. Furthermore, no alterations in blood glucose levels, body weight, or adiposity were observed. These findings suggest that ectopic UCP1 in the liver dissipates surplus energy without affecting required energy and exerts minimal metabolic effects in lean mice. Thus, enhanced UCP expression in the liver is a new potential therapeutic target for the metabolic syndrome.
 ...
PMID:Dissipating excess energy stored in the liver is a potential treatment strategy for diabetes associated with obesity. 1567 88

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

Dietary fat is considered an important contributing factor in the obesity epidemic, and high-fat diets are used widely to induce obesity and diabetes-related traits in susceptible rodent strains. Little attention, however, is usually paid to the interaction of fat with the other macronutrients. The aim of this study, therefore, was to investigate the effects of high-fat, isoenergetic diets with different protein:carbohydrate (CHO) ratios on obesity, energy metabolism, and glucose homeostasis in mice. Male adult C57BL/6J mice consumed ad libitum for 10 wk a control diet (41:42:17 ratio of CHO:protein:fat, 15.5 kJ/g) or 2 different high-fat diets: high carbohydrate (HC; 41:16:43, 17.7 kJ/g) or low carbohydrate (LC; 11:45:44, 17.5 kJ/g). Body weight and fat gains were rapid and were greater in HC mice than in other groups due to an initial pronounced hyperphagia and subsequent passive overconsumption. Weight and fat gains were less in LC mice but still greater than in controls. Energy expenditure was not affected by the diets, and total energy intake explained 84% of the variation in final body weight. The respiratory quotient was lower in LC mice than in other groups, indicating high fat oxidation rates due to the LC diet. Blood glucose was lower and insulin sensitivity greater in LC mice than in HC mice. We conclude that increasing the protein:CHO ratio in a high-fat diet delays but does not prevent the development of adiposity. However, glucose homeostasis was improved in LC mice, indicating that a combination of high fat and high CHO is responsible for the development of metabolic syndrome-related traits in mice.
 ...
PMID:Increasing the protein:carbohydrate ratio in a high-fat diet delays the development of adiposity and improves glucose homeostasis in mice. 1604 8

Hummingbirds and other nectar-feeding, migratory birds possess unusual adaptive traits that offer important lessons concerning obesity, diabetes and the metabolic syndrome. Hummingbirds consume a high sugar diet and have fasting glucose levels that would be severely hyperglycemic in humans, yet these nectar-fed birds recover most glucose that is filtered into the urine. Hummingbirds accumulate over 40% body fat shortly before migrations in the spring and autumn. Despite hyperglycemia and seasonally elevated body fat, the birds are not known to become diabetic in the sense of developing polyuria (glucosuria), polydipsia and polyphagia. The tiny (3-4 g) Ruby-throated hummingbird has among the highest mass-specific metabolic rates known, and loses most of its stored fat in 20 h by flying up to 600 miles across the Gulf of Mexico. During the breeding season, it becomes lean and maintains an extremely accurate energy balance. In addition, hummingbirds can quickly enter torpor and reduce resting metabolic rates by 10-fold. Thus, hummingbirds are wonderful examples of the adaptive nature of fat tissue, and may offer lessons concerning prevention of metabolic syndrome in humans.
 ...
PMID:Adipose energy stores, physical work, and the metabolic syndrome: lessons from hummingbirds. 1635 26

An interactive network comprised of neuropeptide Y (NPY) and cohorts is obligatory in the hypothalamic integration of appetite and energy expenditure on a minute-to-minute basis. High or low abundance of NPY and cognate receptors dysregulates the homeostatic milieu engendering hyperphagia, decreased energy expenditure, obesity and attendant metabolic syndrome cluster of dyslipidemia, glucose intolerance, insulin resistance and hyperinsulinemia, risk factors for type II diabetes and cardiovascular diseases. Increasing the supply of the endogenous repressor hormone leptin locally in the hypothalamus with the aid of leptin gene therapy, blocked age-related and dietary obesities, and the sequential development of dyslipidemia, hyperglycemia, and insulin resistance. Thus, sustained repression of NPY signaling with increased leptin selectively in the hypothalamus can avert environmental obesity and the risks of metabolic diseases.
 ...
PMID:Subjugation of hypothalamic NPY and cohorts with central leptin gene therapy alleviates dyslipidemia, insulin resistance, and obesity for life-time. 1638 5

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

Overeating and obesity are major health problems even in the elderly since they lead to the metabolic syndrome, resulting in an increase in cardiovascular disease. The development of novel nutritional therapeutics for the purpose of promoting health and controlling ageing process aims at the self-helping elderly. Caloric restriction (CR) has been widely investigated as a powerful method that can prevent and reverse senescent changes. CR might counteract the deleterious aspects of metabolic syndrome and may prolong lifespan even in humans. However, we should keep in mind that several fundamental issues about CR still remain unsolved. In addition, malnutrition and nutritional troubles are emerging problems in the elderly in care. Thus, we emphasize that nutritional intervention aiming at ageing control should be established and be developed as a custom-made therapeutics for the elderly, who show great individual variation.
 ...
PMID:[Potential and unsolved problems concerning caloric restriction in nutritional therapeutics for the purpose of promoting health and controlling aging]. 1652 13

The metabolic syndrome (MS) is a cluster of metabolic abnormalities with insulin resistance as a major characteristic. The main adverse consequence of the MS is cardiovascular disease (CVD). Complex, mutually reinforcing interactions between obesity and insulin resistance largely account for the pathogenesis of MS. Central pathophysiologic features include: insulin resistance, atherogenic dyslipidemia, chiefly present as low HDL-C together with increases in triglycerides and small dense, low density lipoprotein particles, hypertension, a proinflammatory state, with increases in acute-phase reactants, and a prothrombotic state. Although lifestyle and overeating seem to be the triggering pathogenic factors, genetic elements are also involved in the pathogenesis of MS. When present, insulin resistance results in impaired insulin action in insulin-sensitive tissues such as muscle, fat, and liver. Insulin resistance results in abnormalities of glucose metabolism, with reduced peripheral disposal of glucose in muscle and increased hepatic glucose output in the fasting state. But, most importantly, the progressively increasing concentration in circulating glucose leads to various abnormalities in insulin secretion. Elevated insulin levels themselves are atherogenic by inducing an oxidative stress and by stimulating sympathetic-nerve activity. Ectopic fat deposition, stress, proinflammatory state, and a maladaptive response of innate immunity may together concur to the development of the MS. When this condition is acknowledged, substantial modification of life style and correction of each single risk factor should be pursued without uncertainties and without hierarchical approach; this means that each risk factor should be treated and brought to target.
 ...
PMID:Insulin resistance: trigger or concomitant factor in the metabolic syndrome. 1663 26


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