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

The aim of this paper is to assess the clinical effectiveness of orlistat used for the management of obesity. Nineteen electronic databases were searched for randomized controlled trials evaluating the effectiveness of orlistat for weight loss or maintenance of weight loss in overweight or obese patients. Each included trial was assessed for methodological quality. Statistical pooling was performed when trials were considered to be sufficiently similar. Twenty-three trials were eligible for inclusion. Placebo-controlled trials recruiting patients with uncomplicated obesity reported statistically significant differences in favour of orlistat for weight loss and changes in obesity-related risk factors at all time points. Trials in obese patients with defined risk factors at baseline showed similar results, however, smaller effect sizes were observed in patients with type 2 diabetes. The effectiveness of orlistat relative to other anti-obesity drugs is currently unclear. When orlistat was added to simvastatin, this proved to be more effective for weight loss than either drug used individually. Orlistat use is associated with a higher incidence of gastrointestinal adverse events compared with placebo. In conclusion, orlistat is more effective than placebo in promoting weight loss, maintenance of weight loss, and improving cardiovascular risk factor profiles. Baseline parameters of patients seen in clinical practice should be taken into account when considering treatment.
 ...
PMID:A systematic review of the clinical effectiveness of orlistat used for the management of obesity. 1496 7

A case report of abuse of the anti-obesity drug, Orlistat, is reported in a normal-weight woman with an eating disorder and stimulant dependence. The case is discussed with reference to the availability of prescription drugs on the Internet, abuse of nonamphetamines and the side effect profile of Orlistat versus laxatives.
 ...
PMID:Case report of abuse of Orlistat. 1500 Oct 13

One of the fundamental principles of pharmacology is that most drugs have side effects. Although considerable attention is paid to detrimental side effects, drugs can also have beneficial side effects. Given the time and expense of drug development, it would be particularly exciting if a systematic method could be applied to reveal all of the activities, including the unappreciated actions, of a potential drug. The present study takes the first step along this path. An activity-based proteomics strategy was used to simultaneously identify targets and screen for their inhibitors in prostate cancer. Orlistat, a Food and Drug Administration-approved drug used for treating obesity, was included in this screen. Surprisingly, we find a new molecular target and a potential new application for Orlistat. Orlistat is a novel inhibitor of the thioesterase domain of fatty acid synthase, an enzyme strongly linked to tumor progression. By virtue of its ability to inhibit fatty acid synthase, Orlistat halts tumor cell proliferation, induces tumor cell apoptosis, and inhibits the growth of PC-3 tumors in nude mice.
 ...
PMID:Orlistat is a novel inhibitor of fatty acid synthase with antitumor activity. 1502 45

We describe a line of transgenic rats in which the males develop a unique autosomal dominant, late-onset obesity (LOB) phenotype. LOB males gradually accumulate fat specifically in visceral, but not peripheral, fat depots despite a normal intake of a low fat diet. LOB females normally develop only mild obesity with advanced age. However, the phenotype can be induced rapidly in young females by ovariectomy and prevented by estrogen replacement. LOB males are highly sensitive to dietary fat. Young, nonobese LOB males gain more weight on a 30% fat diet and lose more weight when treated with the lipase inhibitor, Orlistat, than their nontransgenic littermates. Remarkably, despite severe visceral obesity, LOB rats have normal fasting blood glucose, insulin, and corticosterone; show normal or increased insulin sensitivity in glucose and insulin tolerance tests; have increased plasma adiponectin levels; and display a heightened response to treatment with rosiglitazone. Their visceral adiposity reflects a specific increase in visceral adipocyte number, not size. Analysis of the transgene in LOB rats revealed a deletion in the gene encoding the S26 subunit of the mitochondrial ribosome that results in the production of a truncated protein, which we show to be imported into mitochondria. However, the transgene integrant is complex, so whether this is the sole molecular disruption underlying this phenotype remains to be established. Nevertheless, LOB rats provide a valuable new model of late-onset, male-preponderant, visceral-specific obesity, clearly dissociated from insulin resistance.
 ...
PMID:Visceral obesity without insulin resistance in late-onset obesity rats. 1503 13

In eukaryotes, fatty acid synthase (FAS) is the enzyme responsible for synthesis of palmitate, the precursor of long-chain nonessential fatty acids. FAS is up-regulated in a wide range of cancers and has been suggested as a relevant drug target. Here, two independent approaches are taken toward knocking down FAS and then probing its connection to tumor cell proliferation. In one approach, Orlistat, a drug approved for treating obesity, is used as a potent inhibitor of the thioesterase function of FAS. In a separate strategy, the expression of FAS is suppressed by targeted knock-down with small interfering RNA. In both circumstances, the ablation of FAS activity causes a dramatic down-regulation of Skp2, a component of the E3 ubiquitin ligase that controls the turnover of p27Kip1. These effects ultimately tie into the retinoblastoma protein pathway and lead to a cell-cycle arrest at the G1/S boundary. Altogether, the findings of the study reveal unappreciated links between fatty acid synthase and ubiquitin-dependent proteolysis of cell-cycle regulatory proteins.
 ...
PMID:A fatty acid synthase blockade induces tumor cell-cycle arrest by down-regulating Skp2. 1513 78

In the normal population, the prevalence of obesity is almost 20%. It is a condition influenced by genetic factors, so that individual behavior cannot be regarded as its sole cause. The amount of food is essentially determined by the hormone leptin, the feedback regulation of which can be disturbed by a modification of the molecule or a mutation of the receptor. A further important determinant is energy consumption, which is subject to large individual variations, which partly result from thermogenesis. With regard to the fat distribution, it is concentrated on the trunk in the android form as compared to the hips in the gynecoid form. The android form is subject to a higher incidence of cardiovascular morbidity and mortality. The indirect determination of body fat by measuring the body mass index (weight [kg]/body weight [m(2)]) is hence less reliable than measuring the waist (women > 80 cm, men > 94 cm). The effects of generalized obesity on cardiovascular function are chiefly an increase of blood volume and an eccentric left ventricular hypertrophy. This first of all results in diastolic dysfunction, which can give rise to a disturbance of systolic function in left ventricular dilatation. Concentric hypertrophy develops in the presence of arterial hypertension. This is twice as frequent in obese patients than in the normal population, which is due to increased activity of the sympathetic nervous system and stimulation of the renin-angiotensin system. A disturbance of lipid metabolism is observed four to six times more frequently. The qualitative change in LDL fraction with a raised concentration of low density LDL particles appears to be of crucial importance. With increasing fat mass, the sensitivity to insulin is lowered, so that in obesity the risk of developing diabetes mellitus type 2 is tripled. Since there has been a dramatic increase in the numbers of overweight children and adolescents (from 10.5% to 15.5% within the past five years), prevention programs should be started in good time. A reduction in calorie intake and an altered dietary composition (55% complex carbohydrates, 30% fat and 15% to 20% protein) on the one hand, and increased physical activity on the other hand continue to be the central components. The latter is especially effective when it regularly gives rise to an increased turnover of fatty acids as a result of an increased energy metabolism at moderate intensity. This leads to adaptation, i. e. an increase in the activity of lipoprotein lipase. If prevention programs and/or changes in lifestyle do not give rise to the desired weight reduction, medication is indicated in some adults. Sibutramine (Reductil and orlistate (Xenical) lead to an additional weight loss of up to 10%. However, consistent treatment of any cardiovascular risk factors present is more important. Treatment of arterial hypertension is of greatest prognostic significance, especially in concomitant diabetes mellitus. In individual cases and after thorough discussion of indication surgical options should be considered.
 ...
PMID:[Obesity and cardiovascular diseases-theoretical background and therapeutic consequences]. 1524 61

The conventional cardiovascular risk factors such as smoking, hyperlipoproteinemia, arterial hypertension and diabetes are responsible for nearly 75% of myocardial infarction events. Since obesity is associated with a two- or threefold increased risk for arterial hypertension and diabetes, the reduction of body weight presents a basic and causal approach. Indeed 60% of the German population is overweight, and every fifth person has obesity. A low-calorie diet and higher quality nutrition as well as increased physical activity is the main therapeutic strategy. The maximum fat supply in a 1200 kcal/d diet should be less than 70 g. Training should be of low intensity, below the anaerobic threshold (50-70% of VO2max), in order to obtain optimal metabolic effect in combination with maximal fat reduction. Should the newly adopted lifestyle not result in a satisfactory loss of weight, medication can be applied in addition. Sibutramin (Reductil) or Orlistat (Xenical) can in individual cases be of help and lead to a further weight loss of up to 10%. It has been demonstrated that such weight loss can evoke the same positive effects of glucose metabolism in patients with impaired glucose tolerance as can metformin. Nevertheless, from a prognostic point of view, in patients with coronary artery disease and manifest diabetes, insulin therapy is required. Although arterial hypertension carries with it four times the risk of stroke and twice that of myocardial infarction, the majority of the population does not receive adequate treatment. Even after an acute cardiac event, in every second patient, an elevated blood pressure of > 140/90 mm Hg at the beginning of the rehabilitation period is found. In approximately 80% of the patients, a guideline-based therapy can be achieved during the follow-up phase. Comparable results apply to LDL-cholesterol patients as well. For patients with chronic coronary artery disease, it is highly important that medication and change in lifestyle be continued. Patients need to receive standardized information and ongoing medical care.
 ...
PMID:[Modification of conventional risk factors in coronary artery disease]. 1528 4

Co-existence of obesity and type 2 DM exacerbates metabolic and other remediable health consequences further. Various pharmacological therapies have been adopted when changing of lifestyle fail to achieve target glycaemic control. Our objective is to find out whether Orlistat can reduce both weight and need for oral hypoglycaemic agent (OHA) and improves glycaemic status,lipid disorders, blood pressure in Bangladesh type 2 DM with obesity. In this center, open-label, randomized, controlled pilot trial 36 type 2 patients with obesity were enrolled. All patients aged 40-65 years had BMI >25 kg/m2 taking sulfonylureas and hypocalorie diet. Twenty one randomly cases were treated with orlistat 120 mg three times daily for 6 months and 15 without orlistat as control. Body weight, waist circumferances, fasting blood sugar, HbAlc,serum lipids, blood pressure and dose of drugs were monitored at 0,12, 24 weeks. After 6 months, orlistat group showed non-significant weight loss than control group (3.95% vs 1.42% from base lines), but showed significant reduction of waist circumference (6 % vs 0.63 %, p<0.01 vs p>0.05 from base line). Orlistat group had significant improvement in glycaemic status (HbA1c changes: 22.37% vs 13.38%, p<0.001 vs p>0.05 and FBS changes: 21.76% vs 22.95%, p<0.01vs p<0.05). Lipid profile had reduced significantly from base lines (Chol: 19.31% vs 9.12%,p<0.001vs >0.05; LDL Chol: 24.99% vs 19.09%, p<0.001 vs p<0.01; Triglyceride: 34.48% vs 12.61%, p<0.001 vs p>0.05). Diastolic pressure had improved significantly in orlistat group (6.73% vs 3.70%, p<0.01 vs >0.05). Reduction of OHA doses were found in both groups. Thus orlistat can be used as an adjuvant therapy with other OHA in managing glycaemic control, lipid profiles and blood pressure.
 ...
PMID:Orlistat as an adjunct therapy in type 2 obese diabetic patients treated with sulphonylurea: a Bangladesh experience. 1537 63

The pharmacological treatment of obesity should be considered when cannot be achieved a 10% weight loss with diet therapy and physical activity. The drugs effective in obesity treatment may act by different mechanisms such as reduction in food intake, inhibition of fat absorption, increase of thermogenesis and stimulation of adipocyte apoptosis. At present, we only have two marketed drugs for obesity treatment. Sibutramine is an inhibitor of norepinephrine, dopamine and serotonina reuptake which inhibits food intake and increases thermogenesis. Sibutramine administration for a year can induce a weight loss of 4-7%. Its main side effects are hypertension, headache, insomnia and constipation. Orlistat is an inhibitor of pancreatic lipase which is able to block the absorption of 30% of ingested fat. Its administration induces weight loss and reduction of ulterior weight regain. Also, this drug improves hypertension dyslipdaemia and helps to prevent diabetes in 52% of cases when administered over four years. The increase in frequency of stools and interference with vitamin absorption are its main side effects. Glucagon-like peptide 1, which increases insulin sensitivity and satiety, adiponectin and PPAR-gamma agonists which reduce insulin resistance and modulates adipocyte generation are the basis for future therapeutic approaches of obesity. Phosphatase inhibitors induce PPAR-gamma phosphorylation and UCP-1 expression leading to an increase in thermogenesis and reduction in appetite.
 ...
PMID:[Pharmacological treatment of obesity]. 1538 15

Orlistat is an inhibitor of gastrointestinal lipases and, therefore, prevents the absorption of dietary fat. This agent reduces weight in obese adults and adolescents with or without comorbidities (including type 2 diabetes mellitus, hypercholesterolaemia, hypertension, metabolic syndrome) who received up to 4 years of therapy in conjunction with a hypocaloric diet. In obese patients, orlistat in combination with a hypocaloric diet improved metabolic risk factors and reduced the risk of developing type 2 diabetes. Furthermore, this agent was cost effective in patients with obesity, particularly those with type 2 diabetes. Orlistat is generally well tolerated, with gastrointestinal adverse events being most commonly reported. Orlistat, in addition to lifestyle and dietary intervention, is thus an attractive option for the treatment of patients with obesity, especially those with associated comorbidities or at risk of developing type 2 diabetes.
 ...
PMID:Orlistat: a review of its use in the management of patients with obesity. 1556 54


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