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

The JCR:LA-cp rat is one of a number of strains incorporating the autosomal recessive cp gene that induces obesity. This strain is unique in the development of not only a profound insulin resistance, but an accompanying cardiovascular disease that correlates strongly with hyperinsulinemia. The hyperinsulinemia develops rapidly after 4 weeks of age, with an age at half-maximum of 5.5 weeks. This reflects postprandial plasma insulin levels that peak at 1000 mU/l in a standardized meal tolerance test. Defective acetylcholine-mediated vascular relaxation develops with a 1-week lag over the developing hyperinsulinemia. The frequency of staining for the vascular adhesion molecules, VCAM-1 and ICAM, does not show either age or genotype variation, although plasma levels do show an age variation. Treatment of the rats with the alpha-glucosidase inhibitor, miglitol (Bay m1099), obviates the exaggerated postprandial glucose and, especially, the insulin responses of the cp/cp rat. This causes an improvement in insulin sensitivity, prevention of the impaired vascular relaxation, and reduction in plasma levels of advanced glycated end-products. Arterial wall morphology, as visualized by both scanning and transmission electron microscopy, shows abnormal endothelium, adherent macrophages, and activated migrating smooth muscle cells in the intima. Oil-Red-O staining reveals lipid deposits in the intimal spaces, as confirmed by the presence of foam cells. The lesions resemble fatty streaks or modest atherosclerosis in man, rather than the extensive cholesterol-laden lesions seen in familial hypercholesterolemia or cholesterol-fed rabbit models. The lean rats of the strain show similar, but less marked, intimal abnormalities. The vasculopathy in this animal model appears to be precipitated by the developing hyperinsulinemia, but also requires an underlying abnormality of vascular smooth muscle and possibly also of the endothelium.
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PMID:Vasculopathy and insulin resistance in the JCR:LA-cp rat. 967 79

Upregulation of endothelial adhesion molecules is the earliest step of atherogenesis. Whether obesity induces endothelial adhesin upregulation is unknown. To address this topic, circulating vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, and von Willebrand factor (vWF) concentrations were evaluated in 22 obese hypertensive (51.4+/-4.6 years [mean+/-SD age]), 19 obese normotensive (50.6+/-3.8 years), 18 nonobese hypertensive (52.3+/-3.9 years), and 16 nonobese normotensive (52. 4+/-3.5 years) men without other risk factors or overt atherosclerosis. All measurements were repeated in the obese subgroups after weight loss induced by 12 weeks of caloric restriction. Basal circulating VCAM-1 levels were similar between the 2 obese groups but were higher (P<0.0001) than in the 2 nonobese groups. No differences were found between nonobese hypertensives and normotensives. Serum low density lipoprotein cholesterol was weakly correlated with plasma soluble VCAM-1 levels in pooled, obese subjects (r=0.362, P=0.02). Plasma soluble adhesin and vWF concentrations decreased significantly after weight loss in obese hypertensives (VCAM-1 P=0.03, ICAM-1 P=0.004, E-selectin P<0.0001, and vWF P=0.003) and normotensives (VCAM-1 P=0.04, ICAM-1 P=0.003, E-selectin P<0.0001, and vWF P<0.0001). Body mass index was correlated with plasma E-selectin concentrations at baseline and after weight loss in obese hypertensives (r=0.501, P=0.018 and r=0. 466, P=0.03, respectively) and obese normotensives (r=0.523, P=0.021 and r=0.460, P=0.05, respectively). In conclusion, our data show that obesity per se induces early endothelial activation in hypertensive and normotensive men. Weight loss counteracted endothelial activation in both obese hypertensive and normotensive men.
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PMID:Early upregulation of endothelial adhesion molecules in obese hypertensive men. 1052 28

One of the traits of type I and II diabetes lies in the presence of extensive rheological disorders. Rheological changes appear during infancy, mainly in type I diabetes: decreased red cell deformability, leukocyte rigidity, monocyte activation, alteration in microvessel flux (sludge) and functions. Such disorders are however sensitive to insulin and metabolic correction for a long period. Macrorheological disorders develop at the time of puberty and when lipid changes and vascular complications appear (hypertension, visceral obesity, atherosclerosis). Such changes have potent effects on diabetic arteriopathy, as shown by altered TcPO(2). Numerous medical teams are taking into account red cell aggregation measurements reflecting post-capillary flux behavior. In addition, a proposed score may be used based on fibrinogen, hematocrit, triglycerides as viscosity acting factors, and endothelial markers, Willebrand factor and VCAM-1. An increased score is an indication of suspected distal functional alteration of microvessels.
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PMID:[Are rheological markers of poor prognosis present in diabetic arteriopathies?]. 1131 17

The aims of this study were to elucidate the factors that contribute to endothelial activation and fibrinolytic abnormalities in patients with poorly controlled type 2 diabetes and to determine whether improved glycemic control reduces endothelial activation. Adhesion molecules [E-selectin, intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1], von Willebrand factor, total nitric oxide (NO), endothelin-1, tissue plasminogen activator, and plasminogen activator inhibitor-1 were measured in 43 type 2 diabetic subjects with hemoglobin A1c of 9.0% or more at baseline (compared with 21 healthy controls) who after 20 wk had been randomized to either improved (IC) or usual (UC) glycemic control. At baseline, type 2 diabetic patients had significant endothelial activation and abnormal fibrinolysis compared with control subjects. Body mass index in the diabetic patients was the only independent predictor of E-selectin (P = 0.007), ICAM-1 (P = 0.01), and NO (P = 0.008) concentrations, but not vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, or tissue plasminogen activator (all P > 0.05). Type 2 diabetic patients with a body mass index of 28 kg/m2 or less had concentrations of E-selectin, ICAM-1, endothelin-1, and NO similar to those in healthy controls. After 20 wk, hemoglobin A1c was significantly lower in IC vs. UC (IC, 8.02 +/- 0.25%; UC, 10.23 +/- 0.23%; P < 0.0001), but there were no significant changes in markers of endothelial activation or indexes of fibrinolysis. Obesity appears to be the most important predictor of endothelial activation in patients with type 2 diabetes. Short-term improvement in glycemic control does not appear to reduce endothelial activation.
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PMID:The influences of obesity and glycemic control on endothelial activation in patients with type 2 diabetes. 1170 27

To investigate the relationships between serum concentrations of soluble adhesion molecules and hyperglycemia, insulin resistance, or other conventional risk factors in type 2 diabetes, we measured soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), insulin sensitivity, and conventional risk factors in 150 Japanese type 2 diabetic patients without apparent diabetic macroangiopathy. High serum concentrations of sVCAM-1 and sE-selectin were observed in patients with type 2 diabetes. Serum concentrations of soluble adhesion molecules were not significantly influenced by sex, hypertension, dyslipidemia, or microangiopathy. Spearman correlation showed that sVCAM-1 concentrations correlated significantly with fasting plasma glucose (FPG), fasting C-peptide, and insulin sensitivity [K index of the insulin tolerance test (K(ITT))] (rho=0.19,0.23, and -0.23, respectively). Soluble E-selectin concentrations correlated significantly with body mass index (BMI), FPG, fasting C-peptide, insulin sensitivity, and triglyceride (rho=0.33,0.42,0.26,-0.48, and 0.29, respectively). Multiple regression analysis showed that FPG, fasting C-peptide, and total cholesterol were independent factors that correlated with sVCAM-1 levels. BMI, FPG, and insulin sensitivity were independent factors that correlated with sE-selectin levels. Serum concentrations of sE-selectin significantly increased associated with clustering of conventional risk factors those obesity, hypertension, dyslipidemia, and current smoking (P<0.01). Thus, sVCAM-1 and sE-selectin levels are related to both hyperglycemia and insulin resistance. Soluble E-selectin levels may be related to obesity, hyperglycemia, and insulin resistance and may reflect the presence of a multiple risk factor clustering syndrome.
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PMID:Serum concentrations of soluble adhesion molecules are related to degree of hyperglycemia and insulin resistance in patients with type 2 diabetes mellitus. 1179 79

Serum concentrations of soluble adhesion molecules, eg, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin are elevated in patients with type 2 diabetes. However, little is known about the role of obesity or abnormal fat distribution in inducing upregulation of adhesion molecules. To investigate this issue, soluble ICAM-1, VCAM-1, and E-selectin levels were evaluated in 40 obese and 30 nonobese patients with type 2 diabetes. Both groups were matched for age, sex, and glycosylated hemoglobin (HbA(1c)) levels. Computed tomography (CT) was used to measure the abdominal subcutaneous and visceral fat areas. Soluble ICAM-1 and VCAM-1 levels did not differ significantly between obese and nonobese patients. However, serum concentrations of soluble E-selectin were significantly higher in obese than in nonobese patients (90 +/- 7 v 56 +/- 4 ng/mL, P <.01). Soluble E-selectin levels significantly correlated with body mass index, subcutaneous fat area, and visceral fat area (Rho = 0.48, 0.37, and 0.30, respectively). Stepwise multiple regression analysis showed that body mass index (F = 16.7), but not subcutaneous and visceral fat areas (F = 0.29 and 0.01, respectively), significantly and independently correlated with soluble E-selectin levels. Our results suggest that obesity may induce endothelial activation or increased shedding of cell surface E-selectin that leads to subsequent increase in soluble E-selectin levels. The high serum concentrations of E-selectin closely correlated with increased total fat volume, but not with regional fat distribution.
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PMID:High serum concentrations of soluble E-selectin correlate with obesity but not fat distribution in patients with type 2 diabetes mellitus. 1207 44

Metabolic alterations such as insulin resistance are thought to underlie the endothelial dysfunction and low grade inflammation found in morbid obesity. Twenty-six morbidly obese patients, aged 39.0 +/- 10.0 (mean +/- sd), were evaluated before and 4.2 +/- 0.8 months after bariatric surgery. A marked increment in the insulin sensitivity index (S(I)) and the endothelium-dependent vasodilatory response in a dorsal hand vein was observed after weight loss following bariatric surgery. Circulating levels of E-selectin, P-selectin, plasminogen activator inhibitor-1, and von Willebrand factor, which were higher than those in the control group, decreased significantly after surgery. Plasma vascular cell adhesion molecule-1, angiotensin-converting enzyme, intercellular adhesion molecule-1, thrombomodulin, and plasma and intraplatelet cGMP levels did not change after weight loss. All inflammatory markers were higher in morbidly obese patients. After surgery, C- reactive protein and sialic acid diminished, whereas circulating levels of IL-6, TNF-alpha, and its soluble receptors did not. Positive correlations were found between changes in adiposity and S(I) and changes in C-reactive protein and between changes in sialic acid and changes in endothelial function. In conclusion, a marked improvement in S(I), endothelial function, and low grade inflammation was observed in the weight-losing, morbidly obese patients after bariatric surgery. S(I) and adiposity appear to play roles in obesity-related, low grade inflammation that contribute to the endothelial dysfunction observed in morbid obesity.
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PMID:Effects of changes in body weight and insulin resistance on inflammation and endothelial function in morbid obesity after bariatric surgery. 1550 18

Obesity in adulthood is combined with vascular endothelial cell and platelet activation. In this study we evaluated whether or not such activation is already present in obese children. Forty obese (10.3 +/- 2.5 yr) and 40 nonobese (10.3 +/- 2.3 yr) children were studied. Circulating levels of soluble (s) intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin, as indices of vascular endothelial cell activation, were assessed in both groups. Plasma concentrations of sP-selectin and sCD40 ligand, as indices of platelet activation, were also measured. Circulating levels of highly sensitive C-reactive protein (hs-CRP) and the lipid peroxidation product 8-iso-prostaglandin (PG)F(2alpha) were evaluated because of their ability to promote vascular endothelial cell and platelet activation. Circulating levels of all of the assessed markers were higher in obese than in nonobese children (sICAM-1, +38.8 +/- 13.3%; sVCAM-1, +26.5 +/- 13.7%; sE-selectin, +31.3 +/- 17.3%; sP-selectin, +31.7 +/- 16.9%; sCD40 ligand, +36.9 +/- 22.1%; total 8-iso-PGF(2alpha), +24.0 +/- 20.2%; hs-CRP, +76.6 +/- 12.9%; P < 0.0001). Significant correlations (P < 0.004) between plasma total 8-iso-PGF(2alpha) levels and circulating sICAM-1 (r = 0.485), sVCAM-1 (r = 0.506), sP-selectin (r = 0.449), sCD40 ligand (r = 0.498), and hs-CRP (r = 0.520) concentrations were found in obese children. In conclusion, an early activation of vascular endothelial cells and platelets was present in obese children. Increased lipid peroxidation was also present in these children and likely contributed to the observed proinflammatory phenotype.
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PMID:Early activation of vascular endothelial cells and platelets in obese children. 1575 62

Circulating concentrations of inflammatory markers predict cardiovascular disease (CVD) risk and are closely associated with obesity. However, little is known concerning genetic influences on serum levels of inflammatory markers. In this study, we estimated the heritability (h2) of soluble cellular adhesion molecule (sCAM) concentrations and examined the correlational architecture between different sCAMs. The study population included 234 men and 270 women aged 18-76 years, belonging to 121 families participating in the Fels Longitudinal Study. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sESEL-1) and P-selectin (sPSEL-1) were assayed using commercially available kits. A variance components-based maximum likelihood method was used to estimate the h2 of the different serum inflammatory markers while simultaneously adjusting for the effects of known CVD risk factors, such as age and smoking. Additionally, we used bivariate extensions of these methods to estimate genetic and random environmental correlations among sCAMs. Levels of sCAMs were significantly heritable: h2=0.24+/-0.10 for sICAM-1, h2=0.22+/-0.10 for sVCAM-1, h2=0.50+/-0.11 for sESEL-1, and h2=0.46+/-0.10 for sPSEL-1. In addition, a significant genetic correlation (rho(G)=0.63) was found between sICAM-1 and sVCAM-1 indicating some degree of shared genetic control. In the Fels Longitudinal Study, the levels of four sCAMs are significantly influenced by genetic effects, and sICAM-1 shares a common genetic background with sVCAM-1.
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PMID:Quantitative genetic analysis of cellular adhesion molecules: the Fels Longitudinal Study. 1600 61

1. In the present study, we sought to determine whether physiological or pathophysiological concentrations of obesity related peptides influence the key early atherogenic events of monocyte adhesion to endothelial cells and adhesion molecule expression using primary human cells. 2. Human umbilical vein endothelial cells were grown to confluence and human monocytes were obtained by elutriation. Adhesion was assessed by automated cell counting and cell adhesion molecule expression (E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) was assayed by ELISA. 3. Experimental conditions included untreated control, ghrelin (100, 150, 450 and 1350 pmol/L), resistin (15, 40 and 100 ng/mL) and combined leptin and insulin (combinations of 30 and 120 pmol/L insulin and 5, 50 and 500 ng/mL leptin). 4. Both resistin and ghrelin produced modest but significant increases in VCAM-1 expression (110 +/- 4 and 117 +/- 13% compared with controls, respectively; both P <or= 0.01). Ghrelin also increased ICAM-1 expression (119 +/- 17% of control; P <or= 0.01). 5. However, despite these increases in adhesion molecule expression, neither ghrelin nor resistin altered monocyte adhesion values. 6. Neither leptin nor insulin altered monocyte adhesion to endothelial cells or cell adhesion molecule expression. 7. Pathophysiologically relevant concentrations of ghrelin and resistin, within the range of concentrations exhibited by patients with anorexia nervosa or the Prader-Willi syndrome and type 2 diabetes, respectively, increase endothelial cell adhesion molecule expression, possibly contributing to increased atherosclerosis risk in such subjects.
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PMID:Pathophysiological levels of the obesity related peptides resistin and ghrelin increase adhesion molecule expression on human vascular endothelial cells. 1617 45


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