Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0028754 (obesity)
124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two syndromes are called syndromes X: cardiac (effort anginal pain, positive exercise tolerance test and absence of angiographically documented critical stenosis in coronary arteries) and metabolic (according to WHO definition: impaired glucose tolerance and insulin resistance and > or = 2 risk factors from the following list: hypertension, dyslipidaemia, visceral obesity and microalbuminuria). Hyperinsulinaemia and endothelial dysfunction are present in both syndromes. The contribution of endothelial nitric oxide synthase gene mutations to the etiology of these syndromes is also studied. Several mechanisms may be involved in the development of endothelial dysfunction, such as reduced synthesis and release of nitric oxide (NO), enhanced inactivation of NO after its release from endothelial cells or enhanced synthesis of vasoconstricting agents. It has been demonstrated that insulin exerts a direct hypertrophic effect on the vascular endothelium and the smooth muscle cells. The hemodynamic properties of insulin have also been discussed. Some findings suggest that in the skeletal muscle circulation, insulin stimulates both endothelin-1 (ET-1) and nitric oxide activity and an imbalance between the release of these two substances may be involved in the pathophysiology of endothelial dysfunction.
...
PMID:[Do syndromes X, cardiac and metabolic, have any similar characteristics?]. 1523 88

Inhibition of hypothalamic nitric oxide (NO) decreases energy intake, and changes in hypothalamic NO synthase (NOS) have been observed in genetically obese rodents, but it is not known if NO is involved in the development of diet-induced obesity (DIO). We therefore measured changes in hypothalamic neuronal NOS (nNOS) in DIO and investigated effects of peripheral and central inhibition of NOS in this model. Expression of nNOS in relation to changes in nutritional state was measured by immunohistochemistry, with radiochemical detection. The effect of chronic intraperitoneal (i.p.) administration of the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day) on energy intake, bodyweight and hypothalamic nitric oxide content was assessed in both chow-fed and DIO animals. Twenty-four hour energy intake after acute intracerebroventricular (i.c.v.) of L-NAME was also measured. Diet-induced obese animals had a statistically significant 32% reduction in the number of nNOS-immunolabelled cells in the ventromedial hypothalamus compared to chow-fed controls. Intraperitoneal administration of L-NAME decreased hypothalamic NO content in both chow-fed and DIO. Energy intake was reduced by 16% in DIO over 16 days, whereas energy intake was only reduced by 11% in chow-fed animals, although both were statistically significant. L-NAME significantly reduced body weight gain in DIO but not in chow-fed rats. L-NAME administered i.c.v. decreased 24 h energy intake to a greater extent in DIO rats, by 18%, compared with a 10% reduction in chow-fed rats. Ventromedial hypothalamic expression of nNOS is sensitive to changes in nutritional state. Despite having reduced nNOS, dietary obese rats were more sensitive to the effects of NOS inhibition than lean controls, suggesting a role for NO in the development of hyperphagia and obesity in rats fed a palatable diet.
...
PMID:Reduced ventromedial hypothalamic neuronal nitric oxide synthase and increased sensitivity to NOS inhibition in dietary obese rats: further evidence of a role for nitric oxide in the regulation of energy balance. 1524 58

Subjects with obesity, family history of type 2 diabetes, polycystic ovary syndrome, previous gestational diabetes, dyslipidemia, hypertension, impaired glucose tolerance or impaired fasting glucose, and those with metabolic syndrome are at risk for the development of type 2 diabetes. Some of them are also at risk for cardiovascular disease. Some underlying abnormalities such as insulin resistance, endothelial dysfunction, and low-grade chronic inflammation are frequently present and closely associated in all these groups. The flow of substrates, hormones, and cytokines from visceral fat to skeletal muscle and to the endothelial cells, along with some genetic abnormalities that lead to impaired insulin action in the peripheral tissues and to impaired insulin-stimulated nitric oxide production in endothelial cells, may play a role in establishing these shared metabolic and vascular derangements. Weight loss, thiazolidinediones, and metformin improve vascular function in subjects at risk for type 2 diabetes and may prove to reduce cardiovascular events in these individuals.
...
PMID:Endothelial dysfunction, inflammation, and insulin resistance: a focus on subjects at risk for type 2 diabetes. 1526 64

Endothelial dysfunction reflects an imbalance of vasodilators and vasoconstrictors. Endogenous endothelin activity seems to be increased in human obesity and type 2 diabetes, and cellular studies suggest that this factor may itself reduce bioavailable nitric oxide (NO). We studied 20 lean, 20 obese, and 14 type 2 diabetic individuals under three protocols, measuring leg vascular responses to intra-arterial infusions of NG-monomethyl-l-arginine (l-NMMA; an inhibitor of NO synthase) alone or in combination with BQ123 (an antagonist of type A endothelin receptors) or phentolamine (used as a control vasodilator). NO synthase inhibition alone (study 1) produced an approximately 40% increase in leg vascular resistance (LVR) in all three participant groups, which was not statistically different across groups (increase in LVR: lean, 135 +/- 28; obese, 140 +/- 32; type 2 diabetic, 184 +/- 51 units; NS). By design, BQ123 at the infused rate of 3 micromol/min produced equivalent approximately 35% reductions in LVR across groups. The subsequent addition of l-NMMA produced a greater increase in LVR among obese participants than lean or type 2 diabetic participants (study 2: lean, 182 +/- 48; obese, 311 +/- 66; type 2 diabetic, 186 +/- 40; P = 0.07). Compared with study 1, the effect of l-NMMA was magnified by BQ123 in obese participants but not in lean or type 2 diabetic participants (P = 0.005, study 1 vs. 2; P = 0.03 for group effect). Phentolamine (75 mg/min) produced vasodilation in obese participants comparable to that seen with BQ123 but failed to augment the L-NMMA response. Endothelin antagonism unmasks or augments NO synthesis capacity in obese but not type 2 diabetic participants. This suggests that impaired NO bioavailability as a result of endogenous endothelin may contribute to endothelial dysfunction in obesity, in addition to direct vasoconstrictor effects of endothelin. In contrast, endothelin antagonism alone is insufficient to restore impaired NO bioavailability in diabetes.
...
PMID:Interactions between endothelin and nitric oxide in the regulation of vascular tone in obesity and diabetes. 1527 86

Epidemiologic studies suggest increased asthma prevalence in obese subjects. However, the relation between obesity and airway inflammation remains unclear. This cross-sectional study aims to investigate the relation between obesity indices and exhaled nitric oxide (ENO) and leukotriene B(4) (LTB(4)) in children with asthma. Asthmatic patients aged 7-18 yr old were recruited. Weight-for-height Z score was calculated from anthropometry. ENO was measured by online single-breath method using a chemiluminescence analyzer, whereas LTB(4) concentrations in exhaled breath condensate (EBC) were quantified using competitive enzyme immunoassay. Ninety-two asthmatics and 23 controls were recruited. The mean ENO and LTB(4) concentrations in EBC were higher in asthmatic patients (87 p.p.b. and 40.5 pg/ml) than controls (25 p.p.b. and 18.7 pg/ml) (p < 0.0001 for both). Obesity, as defined by weight >120% median weight-for-height, was not associated with any alteration in ENO or LTB(4) concentrations in patients with asthma. Besides, these inflammatory markers did not differ between asthmatics in the highest and lowest quartiles of weight-for-height Z score. On multivariate analysis, ENO showed significant correlation with age (beta = 0.511, p < 0.0001), peripheral blood eosinophil count (beta = 0.222, p = 0.019), plasma total IgE concentration (beta = 0.187, p = 0.050) and forced expiratory volume in 1-s (FEV(1); beta = -0.221, p = 0.014). None of the factors was associated with LTB(4) concentration in EBC. In conclusion, ENO and LTB(4) concentration in EBC are increased in childhood asthma. However, these inflammatory markers did not differ between obese and non-obese children with asthma.
...
PMID:The relation between obesity and asthmatic airway inflammation. 1530 44

Although the net balance between vasoconstriction and vasodilation determines the tone of the blood vessel, the vasodilatory-vasoconstrictive response following a challenge may also be determined by the intrinsic mechanical and biological properties of the vascular smooth muscle. This article reviews the action of nitric oxide, acetylcholine,and insulin; the effects of hyperglycemia, increase in free fatty acids, diabetes, and obesity on the vasculature; treatment of hypertension in diabetes; the benefits of lowering blood pressure and intensity of blood pressure control; and compares specific antihypertensive therapies on cardiovascular outcomes. The effects of antihypertensive therapy on microvascular complications, choice of antihypertensive regimen, antioxidant and anti-inflammatory effects of antihypertensive drugs, and the potential role of antidiabetic drugs in the treatment of hypertension are also presented.
...
PMID:Endothelial dysfunction and hypertension in diabetes mellitus. 1530 85

Obesity is associated with increased incidence of cardiovascular mortality. However, the mechanisms that link increased fat mass with hypercholesterolemia, hypertension, endothelial dysfunction and coronary heart disease have not been fully elucidated. Unravelling the diverse neuroendocrine systems, which regulate energy balance and body fat has been a long-standing challenge in biology, with obesity as an increasingly important public health focus. Until recently, the adipocyte has been considered only a passive tissue for the storage of excess energy in the form of fat. However, there is now compelling evidence that adipocytes act as endocrine, secretory cells. It has been shown that several hormones, growth factors and cytokines are actually expressed in white adipose tissue. In a dynamic view of the adipocyte a wide range of signals emanates from white adipose tissue such as tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and their respective soluble receptors. White adipose tissue also secretes important regulators of lipoprotein metabolism like lipoprotein lipase (LPL), apolipoprotein E (apoE) and cholesteryl ester transfer protein (CETP). The increasing number of products secreted by adipocytes also includes leptin, estrogen, angiotensinogen, plasminogen activator inhibitor-1 (PAI-1), tissue factor and transforming growth factor-beta (TGF-beta). Nitric oxide synthase (NOS) has been also reported to be expressed in white adipose tissue. Acylation stimulating protein (ASP), adipophilin, adipoQ, adipsin, monobutyrin, agouti protein and factors related to pro-inflammatory and immune processes have also been shown to be released by white adipocytes. Since blood vessels express receptors for most of the adipocyte-derived factors, adipose tissue seems to play a key role in cardiovascular physiology through the existence of a network of local and systemic signals. The current knowledge in this field will be reviewed in the broader perspective of cardiovascular physiology and pathophysiology.
...
PMID:The adipose tissue as a source of vasoactive factors. 1532 Jul 86

Vascular integrity in the healthy endothelium is maintained through the release of a variety of paracrine factors such as NO (nitric oxide). Endothelial dysfunction, characterized by reduced NO bioavailability, is associated with obesity, insulin resistance and Type II diabetes. Insulin has been demonstrated to have direct effects on the endothelium to increase NO bioavailability. Therefore altered insulin signalling in the endothelium represents a candidate mechanism underlying the association between insulin resistance and endothelial dysfunction. In recent years, it has become apparent that insulin sensitivity is regulated by the adipocytokines, a group of bioactive proteins secreted by adipose tissue. Secretion of adipocytokines is altered in obese individuals and there is increasing evidence that the adipocytokines have direct effects on the vascular endothelium. A number of current antidiabetic strategies have been demonstrated to have beneficial effects on endothelial function and to alter adipocytokine concentrations in addition to their effects on glucose homoeostasis. In this review we will explore the notion that the association between insulin resistance and endothelial dysfunction is accounted for by adipocytokine action on the endothelium. In addition, we examine the effects of weight loss, exercise and antidiabetic drugs on adipocytokine availability and endothelial function.
...
PMID:The role of insulin and the adipocytokines in regulation of vascular endothelial function. 1532 98

The obese Zucker rat is a valuable model for studying kidney disease associated with obesity and diabetes. Previous studies have shown that substitution of animal protein with soy ameliorates the progression of renal disease. To explore the participation of nitric oxide (NO) and caveolin-1 in this protective effect, we evaluated proteinuria, creatinine clearance, renal structural lesions, nitrites and nitrates urinary excretion (UNO(2)(-)/NO(3)V), and mRNA and protein levels of neuronal NO synthase (nNOS), endothelial NOS (eNOS), and caveolin-1 in lean and fatty Zucker rats fed with 20% casein or soy protein diet. After 160 days of feeding with casein, fatty Zucker rats developed renal insufficiency, progressive proteinuria, and renal structural lesions; these alterations were associated with an important fall of UNO(2)(-)/NO(3)V, changes in nNOS and eNOS mRNA levels, together with increased amount of eNOS and caveolin-1 present in plasma membrane proteins of the kidney. In fatty Zucker rats fed with soy, we observed that soy diet improved renal function, UNO(2)(-)/NO(3)V, and proteinuria and reduced glomerulosclerosis, tubular dilation, intersticial fibrosis, and extracapilar proliferation. Renal protection was associated with reduction of caveolin-1 and eNOS in renal plasma membrane proteins. In conclusion, our results suggest that renal protective effect of soy protein appears to be mediated by improvement of NO generation and pointed out to caveolin-1 overexpression as a potential pathophysiological mechanism in renal disease.
...
PMID:Renal protection by a soy diet in obese Zucker rats is associated with restoration of nitric oxide generation. 1532 66

Atherosclerosis is a chronic inflammatory disease which may cause obstructions of the coronary, cerebral and peripheral arteries. It is typically multifactorial, most often dependent on risk factors such as hypercholesterolemia, diabetes, smoking, hypertension, sedentarism, and obesity. It is the single main cause of death in most developed countries due to myocardial infarction, angina, sudden death, and heart failure. Several epidemiological studies suggest that moderate alcohol intake, especially red wine, decrease cardiac mortality due to atherosclerosis. The alcohol effect is described by a J curve, suggesting that moderate drinkers may benefit while abstainers and heavy drinkers are at higher risk. Experimental studies indicate that most beneficial effects of drinking are attributable to flavonoids that are present in red wine, purple grape juice and several fruits and vegetables. The mechanisms include antiplatelet actions, increases in high-density lipoprotein, antioxidation, reduced endothelin-1 production, and increased endothelial nitric oxide synthase expression which causes augmented nitric oxide production by endothelial cells. These findings lead to the concept that moderate red wine drinking, in the absence of contraindications, may be beneficial to patients who are at risk of atherosclerotic cardiovascular events. Moreover, a diet based on fruits and vegetables containing flavonoids may be even more beneficial.
...
PMID:Wine, alcohol and atherosclerosis: clinical evidences and mechanisms. 1533 93


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

---