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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Our previous studies have shown that the dopaminergic D1 receptor agonist SKF38393 (SKF) plus the D2 receptor agonist bromocriptine (BC) act synergistically to reduce obesity in obese C57BL/6J (ob/ob) mice. The present study investigated the effects of this combination on dyslipidemia in ob/ob mice. Female ob/ob mice were treated daily with vehicle or SKF (20 mg/kg body weight [BW]) plus BC (16 mg/kg BW [BC/SKF]) for 14 days. The animals were then used for the characterization of plasma lipoprotein profiles, hepatic triacylglycerol synthesis and secretion, adipocyte lipolysis, adipose and muscle lipoprotein lipase (LPL) activity, and muscle triglyceride (TG) content. The treatment significantly reduced plasma glucose 54%, TG 41%, cholesterol 21%, phospholipid 20%, and free fatty acid (FFA) 36% (P < .01). Hepatic triacylglycerol synthesis was 55% lower in treated mice versus control mice (P < .01). The cell size of isolated adipocytes was significantly reduced (41%) by treatment. LPL activity was increased in soleus skeletal muscle (25%, P < .05) but was sharply reduced in adipose tissue (91%, P < .01) in treated versus control mice. The TG content of hindlimb muscle was about 49% lower in treated versus control mice (P < .05). The basal and isoproterenol-stimulated lipolytic rate was decreased (approximately 53%) in adipocytes from treated animals compared with the control (P < .01). In conclusion, BC/SKF normalized the hypertriglyceridemia likely via its simultaneous antilipogenic action in liver tissue and antilipolytic action in adipose tissue. Decreased plasma flux of FFA partially contributed to the reduced hepatic lipogenesis, plasma very-low-density lipoprotein (VLDL)-TG, and TG in skeletal muscle. The above-described effects of BC/SKF treatment are largely independent of its effect to normalize hyperphagia in ob/ob mice.
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PMID:Bromocriptine/SKF38393 treatment ameliorates dyslipidemia in ob/ob mice. 1045 70

A significant number of Americans are at risk for developing a condition of insulin resistance termed Syndrome X. Dyslipidemia, resistance to insulin, obesity, and blood pressure elevation--the deadly quartet--describe Syndrome X, which increases atherogenic risk and contributes to coronary artery disease. Lifestyle factors such as overeating and physical inactivity play a pivotal role in Syndrome X. This deadly duet has been aptly coined "hyperactive fork" and "hypoactive foot," respectively. In addition, emerging evidence suggests that certain nutrients may help protect against Syndrome X. This review provides a brief discussion of diet and lifestyle factors related to Syndrome X.
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PMID:Syndrome X: medical nutrition therapy. 1086 Mar 97

Prader-Willi Syndrome (PWS) is a multisystemic genetic disease characterized by hypothalamic hypogonadism, mental retardation and compulsive hyperphagia associated with early and severe obesity. Complications of overweight, such as type-2 diabetes Mellitus, dyslipidemia and diffuse atheromatosis are common. We report a 15 years old morbid obese male with PWS, with a body mass index of 57.7 kg/m2, refractory to weight-lowering treatments. He underwent preoperative evaluation and treatment by a multidisciplinary team, and subjected to a 95% gastrectomy, leaving a 50 ml remnant pouch and a long limb (120 cm) Y-Roux gastro-jejuno anastomosis. There were no surgical complications, oral feeding was initiated at the 5th day with an hypocaloric diet. During the first postoperative year, the patient lost 70 kg, achieving a body mass index of 30 kg/m2. Surgical treatment can become a therapeutic choice for obesity in PWS patients.
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PMID:[Prader-Willi Syndrome (PWS) associated to morbid obesity: surgical treatment]. 1287 Feb 38

Prader-Willi syndrome (PWS) is a genetic disorder characterized by mild mental retardation, short stature, abnormal body composition, muscular hypotonia and distinctive behavioural features. Excessive eating causes progressive obesity with increased cardiovascular morbidity and mortality. In the PWS genotype loss of one or more normally active paternal genes in region q11-13 on chromosome 15 is seen. It is supposed that the genetic alteration leads to dysfunction of several hypothalamic centres and growth hormone (GH) deficiency (GHD) is common. PWS is well described in children, in whom GH treatment improves body composition, linear growth, physical strength and agility. Few studies have focused on adults. We examined a cohort of 19 young adults with clinical PWS (13 with positive genotype) and mean BMI of 35 kg/m2. At baseline the activity of the GH-insulin-like growth factor-I (IGF-I) system was impaired with low GH values, low total IGF-I and in relation to the obesity low levels of free IGF-I and non-suppressed IGF-binding-protein-1 (IGFBP-1). 2/3 were hypogonadal. Bone mineral density (BMD) was low. Four patients had impaired glucose tolerance and nine patients high homeostasis model assessment (HOMA) index, indicating insulin resistance. Seven patients had a moderate dyslipidemia. The 13 patients with the PWS genotype were shorter and had significantly lower IGF-I. Seventeen (9 men and 8 women), subsequently completed a 12 months GH treatment trial, and GH had beneficial effects on body composition without significant adverse effects. The effects were more pronounced in the patients with the PWS genotype. Analysis of peptides involved in appetite regulation showed that leptin levels were high reflecting obesity and as a consequence NPY levels were low. In relation to the patients obesity circulating oxytocin levels were abnormally low and ghrelin levels abnormally high. Thus, oxytocin and ghrelin might be involved in the hyperphagia. NPY, leptin and ghrelin did not change during GH treatment. In conclusion this pilot study showed that adults with PWS have a partial GH deficiency, and GH treatment has beneficial effects on body composition in adult PWS without significant side-effects. Larger and longer term studies on the effect of GH replacement in adult PWS are encouraged.
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PMID:Endocrine and metabolic aspects of adult Prader-Willi syndrome with special emphasis on the effect of growth hormone treatment. 1470 May 52

Both in Western countries and in third world countries there is an increasing incidence of obesity. Obesity per se or insulin resistance associated with obesity may increase cardiovascular risk factors including dyslipidemia, hypertension and Type 2 diabetes. Over the past decade the understanding has increased of specific mediators in the hypothalamus that are involved in regulating food intake and body weight. In obese humans fasting plasma lipids can be normal but postprandial lipid metabolism is abnormal with an accumulation of triglyceride-rich remnant lipoproteins. In viscerally obese men chylomicron remnant catabolism was markedly decreased when compared with lean individuals. The decreased clearance of chylomicron remnants in viscerally obese subjects may be explained by competition between chylomicron remnants and the increased hepatic production of VLDL for clearance by low density lipoprotein receptors. Increased food intake in rodent models of obesity was shown to be associated with a delay in the catabolism of remnant lipoprotein particles. Prevention of hyperphagia was found to correct the impairment in the metabolism of remnant lipoproteins. Under fasting and food restricted conditions the improvement of remnant metabolism was associated with an increased oxidation of remnant lipids as determined by a novel stable isotope breath test. Anti-obesity and lipid lowering drugs have been used for the treatment of obesity. Inhibitors of cholesterol synthesis inhibitors (statins) have been shown to be effective in treating dyslipidemia. Inhibition of cholesterol synthesis with Atorvastatin was shown to improve chylomicron metabolism by increasing chylomicron remnant catabolism in obese subjects as assessed by the newly developed stable isotope breath test.
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PMID:Obesity and post-prandial lipid metabolism. Feast or famine? 1502 94

Patients with hypopituitarism develop a phenotype similar to metabolic syndrome with central obesity and diabetes. Similarly, patients with hypothalamic damage may develop central obesity, insulin resistance, and hyperphagia. We sought to examine the clinical associations between hypopituitarism, hypothalamic dysfunction, and nonalcoholic fatty liver disease (NAFLD). A case series of patients seen at our institution with diagnoses of hypopituitarism, hypothalamic obesity, or craniopharyngioma and NAFLD was undertaken. Clinical, laboratory, and liver biopsy features were reviewed. Twenty-one patients were identified. NAFLD was diagnosed 6.4 +/- 7.5 years (median 3 years) after the diagnosis of hypothalamic/pituitary dysfunction. Mean gain in body mass index (BMI) between diagnoses of hypothalamic/pituitary disease and NAFLD was 11.3 +/- 8.9 kg/m(2) at an average yearly rate of 2.2 +/- 2.2 kg/m(2). The majority of patients developed elevated glucose levels and dyslipidemia by time of diagnosis of NAFLD. Of the 10 patients biopsied, six were cirrhotic, two had nonalcoholic steatohepatitis (NASH) with fibrosis, and two had simple steatosis. Long-term follow-up of 66 +/- 33 months (range 12-120) was available for 18 patients. Two required liver transplantation. Six patients died, two from liver related causes. In conclusion, patients with hypothalamic and/or pituitary disease are at risk of excessive weight gain, impaired glucose tolerance, and dyslipidemia with subsequent development of NAFLD. This group has a high prevalence of cirrhosis placing them at risk for liver-related death. The novel evidence that hypothalamic/pituitary dysfunction may be accompanied by progressive NAFLD has important implications for the work-up and management of patients with hypothalamic/pituitary disease.
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PMID:Nonalcoholic fatty liver disease among patients with hypothalamic and pituitary dysfunction. 1505 93

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.
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PMID:Dissipating excess energy stored in the liver is a potential treatment strategy for diabetes associated with obesity. 1567 88

Ectopic fat accumulation has been implicated as a contributing factor in the abnormal metabolic state of obesity. One human model of ectopic fat deposition is generalized lipodystrophy. Generalized lipodystrophy is a rare disorder characterized by a profound deficiency of adipose tissue with resultant loss of triglyceride storage capacity and reduced adipokines, including leptin. Subjects with generalized lipodystrophy and reduced leptin levels often have an increased appetite leading to hyperphagia. Excess fuel consumption, coupled with a lack of adipose tissue, contributes to the significant ectopic triglyceride accumulation in the muscle and liver seen in these subjects. This ectopic fat, along with the deficiency in leptin signaling and perhaps other adipokines, likely contributes to insulin resistance, diabetes, and hepatic steatosis. We report here the long-term effects of leptin replacement in a cohort of these subjects. Fifteen patients with generalized lipodystrophy were treated with twice-daily recombinant methionyl human leptin (r-metHuLeptin) for 12 months. We evaluated metabolic parameters at baseline and every 4 months. Antidiabetes medications were decreased or discontinued as necessary. Reductions were seen in serum fasting glucose (from 205 +/- 19 to 126 +/- 11 mg/dl; P < 0.001), HbA1c (from 9 +/- 0.4 to 7.1 +/- 0.5%; P < 0.001), triglycerides (from 1,380 +/- 500 to 516 +/- 236 mg/dl; P < 0.001), LDL (from 139 +/- 16 to 85 +/- 7 mg/dl; P < 0.01), and total cholesterol (from 284 +/- 40 to 167 +/- 21 mg/dl; P < 0.01). HDL was unchanged (from 31 +/- 3 to 29 +/- 2 mg/dl; P = 0.9). Liver volumes were significantly reduced (from 3,663 +/- 326 to 2,190 +/- 159 cm3; P < 0.001), representing loss of steatosis. Decreases were seen in total body weight (from 61.8 +/- 3.6 to 57.4 +/- 3.4 kg; P = 0.02) and resting energy expenditure (from 1,929 +/- 86 to 1,611 +/- 101 kcal/24 h; P < 0.001). R-metHuLeptin led to significant and sustained improvements in glycemia, dyslipidemia, and hepatic steatosis. Leptin represents the first novel, effective, long-term treatment for severe forms of lipodystrophy.
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PMID:Long-term efficacy of leptin replacement in patients with generalized lipodystrophy. 1598 99

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.
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PMID:Subjugation of hypothalamic NPY and cohorts with central leptin gene therapy alleviates dyslipidemia, insulin resistance, and obesity for life-time. 1638 5


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