Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An open-label, placebo-controlled, randomized, two-way crossover study was performed in 12 healthy volunteers (between 20 and 44 years of age) to assess the effect of orlistat, a gastrointestinal lipase inhibitor that reduces dietary fat absorption and is being developed for weight control in obesity, on the absorption of vitamins A and E. Each participant received a single oral dose of 25,000 IU vitamin A followed 24 hours later by a single oral dose of 400 IU vitamin E on two separate occasions: during oral administration of 120 mg orlistat or placebo three times daily for 9 days. The two treatments were separated by a washout period of at least 2 weeks. Serial blood samples for pharmacokinetic analysis were collected at specified times over 24 hours after each dose of vitamin A for determination of serum concentrations of retinol, and over a period of 5 days after each dose of vitamin E for determination of serum concentrations of alpha-tocopherol, total cholesterol, and triglycerides. Orlistat significantly reduced the absorption of vitamin E (approximately 43% according to maximum concentration and approximately 60% according to area under the concentration-time curve), but not that of vitamin A, at the dose levels studied. The results of this study will aid in the implementation of a vitamin supplementation strategy, should vitamin deficiency occur in patients undergoing orlistat therapy.
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PMID:The effect of orlistat, an inhibitor of dietary fat absorption, on the absorption of vitamins A and E in healthy volunteers. 884 48

Intra-abdominal and subcutaneous adipose tissue display important metabolic differences that underlie the association of visceral, but not subcutaneous, fat with obesity-related cardiovascular and metabolic problems. Because the molecular mechanisms contributing to these differences are not yet defined, we compared by reverse transcription-polymerase chain reaction the expression of 15 mRNAs that encode proteins of known importance in adipocyte function in paired omental and subcutaneous abdominal biopsies. No difference in mRNA expression between omental and subcutaneous adipose tissue was observed for hormone sensitive lipase, lipoprotein lipase, 6-phosphofructo-1-kinase, insulin receptor substrate 1, p85alpha regulatory subunit of phosphatidylinositol-3-kinase, and Rad. Total amount of insulin receptor expression was significantly higher in omental adipose tissue. Most of this increase was accounted for by expression of the differentially spliced insulin receptor lacking exon 11, which is considered to transmit the insulin signal less efficiently than the insulin receptor with exon 11. Perhaps consistent with a less efficient insulin signaling, a twofold reduction in GLUT4, glycogen synthase, and leptin mRNA expression was observed in omental adipose tissue. Finally peroxisome proliferator activated receptor-gamma (PPAR-gamma) mRNA levels were significantly lower in visceral adipose tissue in subjects with a BMI <30 kg/m2, but not in obese subjects, indicating that relative PPAR-gamma expression is increased in omental fat in obesity. This suggests that altered expression of PPAR-gamma might play a role in adipose tissue distribution and expansion.
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PMID:Depot-specific differences in adipose tissue gene expression in lean and obese subjects. 942 81

Obesity is common in NIDDM; in a cohort of 314 diabetics in Singapore, 44.3% are overweight. Management of obesity in diabetics differs from that in non-diabetics in that it is more urgent; weight maintenance is more difficult and hypoglycaemic medication may cause weight changes. Like in the non-diabetic, management of obesity in diabetic requires a pragmatic and realistic approach. A team approach is required: the help of the nurse educator, the dietitian, behaviour modification therapist, exercise therapist etc are required. A detailed history, careful physical examination and relevant investigations are required to assess the severity of the diabetic state and to exclude an occasional underlying cause of the obesity in the obese NIDDM. Weight loss is urgent in the obese NIDDM, especially those with android obesity. There must be a reduction in caloric intake. Weight loss leads to improvement in the glucose tolerance, insulin sensitivity, reduction in lipid levels and fall in blood pressure in the hypertensive. Exercise is of limited value except in the younger obese NIDDM. Metformin is the hypoglycaemic drug of choice as it leads to consistent weight reduction. The sulphonylureas may cause weight gain. Insulin should be avoided where possible as it causes further weight gain. Other hypoglycaemic agents include Glucobay (alpha-glucosidase inhibitor) and Troglitazone (insulin sensitizer) which do not alter the weight. Orlistat (lipase inhibitor) is promising as it causes reduction of weight, blood-glucose and lipid levels. Anti-obesity drugs (noradrenergic and serotonergic agents) have modest effects on weight reduction in the obese NIDDM; a widely use preparation, Dexfenfluramine (Adifax) has been withdrawn because of side effects. Surgery such as gastric plication is the last resort in treating the morbidly obese NIDDM. The discovery of leptin in 1994 has led to intense research into energy homeostasis in obesity; hopefully this will lead to better treatment of obesity in diabetics and non-diabetics.
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PMID:Management of obesity in NIDDM (non-insulin-dependent diabetes mellitus). 984 3

Until recently, obesity did not play a major role in considerations of physicians and public health authorities. The impact of health-threatening overweight was so far considered only as a risk factor for various other serious illnesses, such as hypertension, diabetes mellitus, hyperuricemia, elevated blood lipid levels and of vascular diseases of the heart, the brain and the kidneys. Recently however, obesity has been rated by the WHO as an unique disease, resulting in elevated morbidity and mortality. It is of constantly increasing importance because of the raising number of obese individuals in all industrial countries. In Austria an incidence of 8.5% of the adult population is estimated to be obese with a BMI > 30. Though the established concept for treatment of overweight consists of reduction of the caloric intake by diet, there is an obvious need for drugs making dieting easier acceptable to obese patients for prolonged periods. Orlistat is the first representative of a new class of such drugs, inhibiting intestinal acting lipase thus reducing the intestinal absorption of triglycerides; it contributes, therefore, to a reduced calorie intake. Preliminary results of treatment studies with Orlistat are presented, demonstrating its efficacy in inducing weight loss and improving metabolic parameters with tolerable intestinal side effects. After finalization of international studies, demonstrating efficacy and tolerability, orlistat has been registered in Austria in September 1998.
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PMID:[Reduction of obesity and improvement in metabolic parameters by inhibition of intestinal lipases: current results with orlistat]. 987 90

Drugs are part of the multimodal approach of modern obesity treatment. In the near future Sibutramine, a centrally acting serotoninergic and noradrenergic agonist and Orlistat, a peripherally acting lipase inhibitor will be available for treatment of obesity. Since all drugs employed should be applicable for years the latter substance might be especially useful for the mandatory longterm treatment of obese patients.
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PMID:[What is the role of drugs in therapy of obesity?]. 988 2

Besides the classical dietary regimen, it is possible to use specific pharmacological approaches, targeted at the intestine, in order to treat some metabolic disorders. Three approaches will be described: anionic resins for treating hypercholesterolaemia, alpha-glucosidase inhibitors for treating diabetes mellitus and reactive hypoglycaemia, and intestinal lipase inhibitors for treating obesity. All these drugs are based on original concepts, but their clinical use is often limited by the occurrence of digestive side-effects. The latter may generally be reduced by progressive and individual titration of the dosage of each drug and/or by following an appropriate diet.
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PMID:[Drug clinics. How I treat various metabolic diseases treated by a drug intervention that targets the intestine]. 988 53

Catecholamines are the only hormones with pronounced lipolytic action in man. A number of in vivo and in vitro studies suggest that there is lipolytic resistance to catecholamines in subcutaneous adipose tissue, which is the major fat depot in obese subjects. This is due to multiple alterations in catecholamine signal transduction, involving decreased expression and function of beta2-adrenoceptors, increased function of alpha2-adrenoceptors and decreased ability of cyclic monophosphate (AMP) to stimulate hormone sensitive lipase. A sedentary life-style, which usually characterizes obesity, may contribute to the catecholamine resistance. However, hereditary/genetic factors may also be involved. Recently, decreased expression and function of hormone sensitive lipase has been found in subcutaneous adipocytes of non-obese subjects with heredity for obesity. In addition, polymorphisms in the genes for beta2-adrenoceptors, beta3-adrenoceptors and hormone sensitive lipase, associate with obesity. On the other hand, catecholamine-induced lipolysis in visceral adipose tissue is increased in obesity due to increased function of beta3-adrenoceptors (major finding), decreased function of alpha2-adrenoceptors and increased ability of cyclic AMP to stimulate lipolysis. When the findings in different adipose regions are considered together, it appears that there is a redistribution of lipolysis and thereby fatty acid mobilization in obesity, favouring the visceral fat depot. This leads to an increase in the circulating fatty acid levels in the portal vein, which connects visceral fat with the liver. As a consequence, the liver function may be altered leading to hyperinsulinemia, hyperglycemia and dyslipidemia, which usually accompany the obese state.
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PMID:Catecholamine-induced lipolysis in obesity. 1019 56

The pharmacological management of obesity has gained increasing attention as new weight loss treatments are approved and a significant proportion of the public strives to lose weight. Obesity is associated with a high mortality rate, multiple chronic medical conditions, and carries an enormous financial burden. Obesity is a multifactorial condition, most often due to an imbalance in energy intake and expenditure. Despite the greater focus on management of obesity, weight loss remains a difficult goal to achieve. Obesity is a chronic medical condition that may require long term treatment, therefore the risks and benefits of all pharmacological agents must be carefully considered. Noradrenergic appetite suppressants (ie. phenyl-propanolamine, phentermine) result in weight loss but stimulatory effects limit their use. The serotonergic agents (fenfluramine, dexfenfluramine) were effective weight loss drugs, but were voluntarily withdrawn from the US market last year because of cardiovascular and pulmonary complications. The combination noradrenergic/serotonergic agent sibutramine is indicated for the management of obesity, particularly in the presence of other cardiovascular risk factors. Modest weight loss is achieved with sibutramine, although weight gain is significant after discontinuation. In addition, long term safety data are not yet available. The thermogenic combination of ephedrine plus caffeine is minimally effective, and adverse effects are usually transient. Other thermogenic agents, such as beta3-agonists, are still under investigation. Agents may alter digestion through lipase inhibition (orlistat) or fat substitution (olestra). Orlistat decreases systemic absorption of dietary fat, decreasing body weight and cholesterol. Olestra is a fat substitute that has been incorporated into snack foods. Olestra substitution for dietary fat has not been studied as a weight loss strategy, although olestra has no caloric value and may be beneficial. The use of orlistat and olestra may be limited by gastrointestinal adverse effects. Finally, the manipulation of leptin and neuropeptide Y are under investigation for the treatment of obesity. Pharmacological agents should be used as an aid to a structured diet and exercise regimen in the treatment of obesity. Weight loss agents may result in initial weight loss, but sustained weight loss is not always achieved even with continuation of treatment. The effect of weight loss obtained while using pharmacotherapeutic agents on morbidity and mortality has not been established. Therefore, diet and exercise should be the focus of any weight loss programme. There is a continued need for safe and effective pharmacotherapeutic agents for the treatment of obesity.
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PMID:Current concepts in the pharmacological management of obesity. 1040 Apr 3

Today, obesity is the most important modifiable risk factor for type 2 diabetes. An excess of body fat is associated with a deterioration of glucose utilisation and promotes the development of type 2 diabetes, particularly in those with a genetic predisposition for the disease. It is also well established that a reduction of excess body fat improves insulin sensitivity and can prevent the conversion to diabetes. In those with overt diabetes, weight loss usually ameliorates glycaemic control and associated metabolic disturbances. Among the pharmacological agents that are used for the treatment of type 2 diabetes only metformin has a weak weight-lowering activity and is considered as the drug of choice for adjunct pharmacotherapy in obese diabetic subjects. A few studies also suggest that acarbose can induce a modest weight reduction in such patients. In contrast, sulphonylurea and insulin treatment is frequently accompanied by substantial weight gain which should be taken into consideration when these drugs are used. Another approach to improve metabolic control in obese type 2 diabetic patients is the use of weight-lowering agents. The new serotonin and noradrenaline reuptake inhibitor sibutramine promotes weight loss which subsequently leads to improved glycaemic control. Orlistat, a lipase inhibitor, is also able to ameliorate metabolic control in such patients due to its weight-lowering potential. As obesity remains a therapeutic challenge in most type 2 diabetic subjects, weight management drugs may represent an alternative or supplement to antidiabetic agents. Moreover, weight management agents have the advantage that they have additional favourable effects on associated cardiovascular risk factors.
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PMID:The impact of pharmacotherapy on weight management in type 2 diabetes. 1045 66

The prevalence of obesity has doubled in the last 10 years and is now reaching epidemic proportions. There is a significant comorbidity and financial cost associated with this disorder. Orlistat is an intestinal lipase inhibitor that is approved for the treatment of obesity. Recent randomized, double-blind, placebo-controlled trials have demonstrated the benefit of orlistat used in conjunction with a hypocaloric (low-fat) diet in facilitating weight reduction and the long-term maintenance of this weight loss. Patients treated with orlistat lost a greater amount of initial body weight compared to those who received placebo. After 24 months of treatment, weight loss of more than 5% was maintained in a greater number of those treated with orlistat. This was associated with significant reductions in cardiovascular risk factors (cholesterol, LDL cholesterol, LDL:HDL cholesterol ratio). The main adverse events are related to fat malabsorption, with potential losses of fat-soluble vitamins and other compounds. Orlistat as a treatment for obesity, when prescribed within present guidelines, can aid modest weight loss in about one-third of patients. More importantly, it can assist in the maintenance of weight loss with major medical benefits for these patients.
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PMID:Review article: malnutrition and maltreatment--a comment on orlistat for the treatment of obesity. 1046 73


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