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)

Lipoprotein(a) (Lp(a)) is regarded as an independent risk factor for Atherosclerotic cardiovascular disease. The objectives of this study were: to determine the effects of diet and exercise on Lp(a) and to evaluate the relation of Lp(a) with the lipid profile (total serum cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol). Baseline Lp(a), body mass index (BMI) and the lipid profiles were measured in 343 Obese (BMI >30kg/m(2)) African-Americans. After a 3-month intervention of diet and exercise by 105 participants, their lipids were re-measured. Baseline Lp(a) levels ranged from 1.2 to 280mg/dl. Lp(a) was inversely associated with triglyceride (P<0.05). After the intervention, Lp(a) and HDL increased by a mean of 20 and 5%, respectively. Total cholesterol, triglycerides, LDL and BMI decreased by 7, 10, 11 and 8%, respectively. Women taking estrogen replacement had a negligible change in Lp(a) while participants taking HMG-CoA reductase inhibitors had an increase in Lp(a) levels by 30%.
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PMID:Response of lipoprotein(a) levels to therapeutic life-style change in obese African-Americans. 1470 70

Combined hyperlipidemia is increasing in frequency and is the most common lipid disorder associated with obesity, insulin resistance and diabetes mellitus. It is associated with other features of the metabolic syndrome including hypertension, hyperuricemia, hyperinsulinemia and highly atherogenic subfractions of lipoprotein remnant particles including small dense low density lipoprotein-cholesterol. This review examines the mechanisms by which combined hyperlipidemia arises and the various drugs including fibric acid derivatives, hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, and nicotinic acid which can be used either as monotherapy or in combination to manage it and to improve prognosis from atherosclerotic disease in diabetes mellitus, insulin resistant states and primary combined hyperlipidemia. The therapeutic approach to combined hyperlipidemia involves determination of whether the cause is hepatocyte damage or metabolic derangements. Combined hyperlipidemia due to hepatocyte damage should be treated by attention to the primary cause. In the case of metabolic dysfunction because of imbalance in glucose and fat metabolism, therapy of diabetes mellitus and obesity should be optimised prior to commencement of lipid lowering drugs. Both fibric acid derivatives and HMG-CoA reductase inhibitors can be used in the treatment of combined hyperlipidemia with fibric acid derivatives having greater effects on triglycerides and HMG-CoA reductase inhibitors on LDL-C though both have effects on the other cardiovascular risk factors. There is some evidence of benefit with both interventions in mild combined hyperlipidemias and large scale trials are underway. Fibric acid derivatives and HMG-CoA reductase inhibitor therapy can be combined with care, provided that gemfibrozil is avoided, fibric acid derivatives are given in the mornings and shorter half -life HMG-CoA reductase inhibitors are used at night. Combined hyperlipidemia emergencies occur with predominant hypertriglyceridemia in pregnancy or as a cause of pancreatitis. Therapy in the former should aim to reduce chylomicron production by a low fat diet and intervention to suppress VLDL-C secretion using omega-3 fatty acids. In the latter case, fluid therapy alone and medium chain plasma triglyceride infusions usually reduce levels satisfactorily though apheresis may be required. Blood glucose levels also need aggressive management in these conditions. Combined hyperlipidemia is likely to become an increasing problem with the increase in the prevalence of obesity and diabetes mellitus and needs aggressive management to reduce cardiovascular risk.
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PMID:Drug treatment of combined hyperlipidemia. 1472 15

The insulin resistance syndrome represents the co-occurrence of hyperglycaemia, hypertension, central and overall obesity, and dyslipidaemia characterised by low high density lipoprotein-cholesterol (HDL-C) and high triglyceride levels. Epidemiologic studies have revealed an increasing prevalence of the insulin resistance syndrome in elderly populations. Indeed, recent data indicate that over 40% of US adults aged > or =60 years meet current criteria for the insulin resistance syndrome. Patients with this syndrome are at increased risk for the development of both cardiovascular disease (CVD) and type 2 diabetes mellitus, two of the most significant health problems among people >65 years of age. Identification and treatment of the insulin resistance syndrome may thus represent an important approach to reducing the overall burden of morbidity and mortality in the elderly. While development of the insulin resistance syndrome is partly determined by modifiable environmental factors, there may be a genetic basis for the syndrome, with high levels of concordance among monozygotic twins. Ongoing research focusing on the pathophysiology of this syndrome has implicated insulin resistance as the central disorder underlying both the development of diabetes as well as the pro-thrombotic endothelial dysfunction characteristic of CVD. Studies aimed at reversing insulin resistance have identified weight loss, exercise and pharmacological treatment with metformin, thiazolidinediones, HMG-CoA reductase inhibitors (statins) and ACE inhibitors as potential therapies to prevent the development of type 2 diabetes. However, although insulin sensitisation may be beneficial for preventing type 2 diabetes, there are no data yet available to show whether this strategy will reduce the incidence of CVD. Increased exercise and other healthy lifestyle changes form the cornerstone of therapy for elderly patients with the insulin resistance syndrome. In addition, active identification and aggressive management of traditional cardiovascular risk factors are the current standard of care. For elderly patients, recent studies have conclusively demonstrated the safety and efficacy of pharmacological management of elevated blood pressure and cholesterol levels.
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PMID:Should the insulin resistance syndrome be treated in the elderly? 1497 33

The current report describes progress in development of a selective thyroid hormone receptor modulator, GC-1. This compound binds selectively to the beta-isoform of the thyroid hormone receptor, and its uptake into the heart is relatively low. Studies in rats, mice and monkeys show that GC-1 lowers cholesterol with 600- to 1400-fold more potency and approximately two- to threefold more efficacy than atorvastatin, a compound that blocks HMG-CoA reductase. GC-1 also decreases plasma levels of triglyceride and lipoprotein (a), and induces loss of fat. These effects can be observed under conditions where there is either no or minimal effect on heart rate, and no detectable loss of muscle. Although more study is required, compounds of this class deserve further investigation for treating lipid disorders and obesity.
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PMID:Selective activation of thyroid hormone signaling pathways by GC-1: a new approach to controlling cholesterol and body weight. 1510 13

The prevalence of obesity has become increasingly common worldwide, in particular western countries. Obesity, together with insulin resistance, leads to metabolic syndrome in which other coronary risk factors including hyperlipidemia and hypertension cluster in one individual. Hyperlipidemia in metabolic syndrome is characterized increased triglyceride(TG), decreased HDL-C, and small dense LDL, called dyslipidemic triad. Dyslipidemia is attributable to increased flux of free fatty acids to the liver, which promotes TG synthesis, thus VLDL production. Increased VLDL, together with decreased lipoprotein lipase activity due to insulin resistance, causes accumulation of TG-rich lipoproteins, including proatherogenic remnants. Further, increased activities of cholesteryl ester transfer protein and hepatic triglyceride lipase results in low HDL-C and small dense LDL. Initial treatment should be directed to modify life style(weight loss and increased physical activity). Then, pharmacological intervention should be considered when the initial treatment is not fully successful. Fibrate derivatives are considered to be ideal to correct dyslipidemic triad. In addition, potent statins(HMG-CoA reductase inhibitor) can be alternative in metabolic syndrome subjects with elevated LDL-C levels.
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PMID:[Dyslipidemia in metabolic syndrome]. 1520 47

Visceral obesity is frequently associated with high plasma triglycerides and low plasma high density lipoprotein-cholesterol (HDL-C), and with high plasma concentrations of apolipoprotein B (apoB)-containing lipoproteins. Atherogenic dyslipidemia in these patients may be caused by a combination of overproduction of very low density lipoprotein (VLDL) apoB-100, decreased catabolism of apoB-containing particles, and increased catabolism of HDL-apoA-I particles. These abnormalities may be consequent on a global metabolic effect of insulin resistance. Weight reduction, increased physical activity, and moderate alcohol intake are first-line therapies to improve lipid abnormalities in visceral obesity. These lifestyle changes can effectively reduce plasma triglycerides and low density lipoprotein-cholesterol (LDL-C), and raise HDL-C. Kinetic studies show that in visceral obesity, weight loss reduces VLDL-apoB secretion and reciprocally upregulates LDL-apoB catabolism, probably owing to reduced visceral fat mass, enhanced insulin sensitivity and decreased hepatic lipogenesis. Adjunctive pharmacologic treatments, such as HMG-CoA reductase inhibitors, fibric acid derivatives, niacin (nicotinic acid), or fish oils, may often be required to further correct the dyslipidemia. Therapeutic improvements in lipid and lipoprotein profiles in visceral obesity can be achieved by several mechanisms of action, including decreased secretion and increased catabolism of apoB, as well as increased secretion and decreased catabolism of apoA-I. Clinical trials have provided evidence supporting the use of HMG-CoA reductase inhibitors and fibric acid derivatives to treat dyslipidemia in patients with visceral obesity, insulin resistance and type 2 diabetes mellitus. Since drug monotherapy may not adequately optimize dyslipoproteinemia, dual pharmacotherapy may be required, such as HMG-CoA reductase inhibitor/fibric acid derivative, HMG-CoA reductase inhibitor/niacin and HMG-CoA reductase inhibitor/fish oils combinations. Newer therapies, such as cholesterol absorption inhibitors, cholesteryl ester transfer protein antagonists and insulin sensitizers, could also be employed alone or in combination with other agents to optimize treatment. The basis for a multiple approach to correcting dyslipoproteinemia in visceral obesity and the metabolic syndrome relies on understanding the mechanisms of action of the individual therapeutic components.
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PMID:Dyslipidemia in visceral obesity: mechanisms, implications, and therapy. 1528 98

1. Expression levels of four key enzymes of cholesterol metabolism, namely 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, lanosterol 14-demethylase (CYP51), cholesterol 7alpha-hydroxylase (CYP7A1) and sterol 12alpha-hydroxylase (CYP8B1), in metabolic syndrome model rats (SHR/NDmcr-cp) were examined. 2. Decreased expression of CYP51, which may be linked to the development of obesity, was found in the rats. 3. Expression of CYP8B1 was significantly higher in young rats. 4. No substantial change was observed in the mRNA levels of the dominant rate-limiting enzymes of sterol metabolism, namely HMG-CoA reductase and CYP7A1, in the rats. 5. These findings suggest that the expression levels of two key enzymes managing the downstream parts of the cholesterol-metabolizing pathways are altered in the rats, although little change was observed in the expression levels of the dominant rate-limiting enzymes of cholesterol metabolism.
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PMID:Studies on the expression levels of sterol-metabolizing enzymes in the obese model SHR/NDmcr-cp rats. 1564 92

Levan or high molecular beta-2,6-linked fructose polymer is produced extracellularly from sucrose-based substrates by bacterial levansucrase. In the present study, to investigate the effect of levan feeding on serum leptin, hepatic lipogenic enzyme and peroxisome proliferation-activated receptor (PPAR) alpha expression in high-fat diet-induced obese rats, 4-week-old Sprague-Dawley male rats were fed high-fat diet (beef tallow, 40% of calories as fat), and, 6 weeks later, the rats were fed 0%, 1%, 5% or 10% levan-supplemented diets for 4 weeks. Serum leptin and insulin level were dose dependently reduced in levan-supplemented diet-fed rats. The mRNA expressions of hepatic fatty acid synthase and acetyl CoA carboxylase, which are the key enzymes in fatty acid synthesis, were down-regulated by dietary levan. However, dietary levan did not affect the gene expression of hepatic malic enzyme, phosphatidate phosphohydrolase and HMG CoA reductase. Also, the lipogenic enzyme gene expression in the white adipose tissue (WAT) was not affected by the diet treatments. However, hepatic PPARalpha mRNA expression was dose dependently up-regulated by dietary levan, whereas PPARgamma in the WAT was not changed. The results suggest that the in vivo hypolipidemic effect of dietary levan, including anti-obesity and lipid-lowering, may result from the inhibition of lipogenesis and stimulation of lipolysis, accompanied with regulation of hepatic lipogenic enzyme and PPARalpha gene expression.
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PMID:Altered mRNA expression of hepatic lipogenic enzyme and PPARalpha in rats fed dietary levan from Zymomonas mobilis. 1621 30

While diabetes mellitus is most often associated with hypertension, dyslipidemia, and obesity, these factors do not fully account for the increased burden of cardiovascular disease in patients with the disease. This strengthens the need for comprehensive studies investigating the underlying mechanisms mediating diabetic cardiovascular disease and, more specifically, diabetes-associated atherosclerosis. In addition to the recognized metabolic abnormalities associated with diabetes mellitus, upregulation of putative pathological pathways such as advanced glycation end products, the renin-angiotensin system, oxidative stress, and increased expression of growth factors and cytokines have been shown to play a causal role in atherosclerotic plaque formation and may explain the increased risk of macrovascular complications. This review discusses the methods used to assess the development of atherosclerosis in the clinic as well as addressing novel biomarkers of atherosclerosis, such as low-density lipoprotein receptor-1. Experimental models of diabetes-associated atherosclerosis are discussed, such as the streptozocin-induced diabetic apolipoprotein E knockout mouse. Results of major clinical trials with inhibitors of putative atherosclerotic pathways are presented. Other topics covered include the role of HMG-CoA reductase inhibitors and fibric acid derivatives with respect to their lipid-altering ability, as well as their emerging pleiotropic anti-atherogenic actions; the effect of inhibiting the renin-angiotensin system by either ACE inhibition or angiotensin II receptor antagonism; the effect of glycemic control and, in particular, the promising role of thiazolidinediones with respect to their direct anti-atherogenic actions; and newly emerging mediators of diabetes-associated atherosclerosis, such as advanced glycation end products, vascular endothelial growth factor and platelet-derived growth factor. Overall, this review aims to highlight the observation that various pathways, both independently and in concert, appear to contribute toward the pathology of diabetes-associated atherosclerosis. Furthermore, it reflects the need for combination therapy to combat this disease.
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PMID:Diabetes mellitus-associated atherosclerosis: mechanisms involved and potential for pharmacological invention. 1648 46

Patients with peripheral vascular disease are less likely to receive optimal medical management than patients with coronary artery disease. However, early medical treatment is critical because it is profoundly beneficial and the benefits are maximized. Even in patients with advanced disease requiring invasive intervention, medical management has been proven to improve outcome, prolong the success of the intervention, improve functional capacity, and prolong life. The vascular surgeon should be knowledgeable enough to initiate basic medical therapy and to define for their patients the goals that need to be met to optimize their medical management. The vascular surgeon should be instrumental in assuring that the peripheral vascular patient receives medical therapy of the same standard as the patient with coronary disease. The major modifiable risk factors in the vascular patient are: smoking, high blood pressure, hyperlipidemia, physical inactivity, obesity, and diabetes. In addition, the use of beta blockers for patients with coronary disease and antiplatelet therapy as well as angiotensin-converting enzyme (ACE) inhibitors are recommended for all patients with peripheral vascular disease. Statins have favorable effects on multiple interrelated aspects of vascular biology important in atherosclerosis. In particular they have beneficial effects on inflammation, plaque stabilization, endothelial dysfunction, and thrombosis. Statins have also been shown to be beneficial in acute vascular events. Angiotensin-converting enzyme inhibitors have been shown to reduce cardiovascular morbidity and mortality in patients with peripheral arterial disease regardless of the presence or absence of hypertension. A number of the pleiotropic effects of statins are shared by ACE inhibitors. In summary, patients with known vascular disease should be treated aggressively with a combination of a HMG CoA reductase inhibitor, an angiotensin-converting enzyme inhibitor, an antiplatelet agent and a beta blocker if there is a history of coronary disease. They should also receive tight control of their blood pressure and blood sugar. Smokers should be encouraged to stop smoking and should be provided with pharmaceutical and emotional support by their physicians. All of these patients should have their body mass index as close to normal as possible and be on a therapeutic lifestyle diet. Regular aerobic exercise is also indicated. Patients with symptomatic claudication should be considered for cilostazol. Patients with multiple risk factors for vascular disease, but who do not have documented disease should also be on statin therapy. As more studies define the linear relationship between lower LDL-C levels and lowered risk of vascular events, indicating that the lower the LDL-C level, the lower the risk, experts are advocating more aggressive lipid-lowering therapy. In patients with peripheral arterial disease, some experts now advocate lowering the goal of LDL therapy to 70 mg/dL.
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PMID:Optimal medical management of peripheral arterial disease. 1727 51


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