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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity, a state of increased adipose tissue mass, is a major cause for type 2 diabetes, hyperlipidemia, and hypertension, resulting in clustering of risk factors for atherosclerosis. Heterozygous PPARgamma knockout mice and KKA(y) mice administered with a PPARgamma antagonist were protected from high-fat diet-induced adipocyte hypertrophy and insulin resistance. Moderate reduction of PPARgamma activity prevented adipocyte hypertrophy, thereby diminution of TNFalpha, resistin, and FFA and upregulation of adiponectin and leptin. These alterations led to reduction of tissue TG content in muscle/liver, thereby ameliorating insulin resistance. Insulin resistance in the lipoatrophic mice and KKA(y) mice were ameliorated by replenishment of adiponectin. Moreover, adiponectin transgenic mice ameliorated insulin resistance and diabetes, but not the obesity of ob/ob mice. Furthermore, targeted disruption of the adiponectin gene caused moderate insulin resistance and glucose intolerance. In muscle, adiponectin activated AMP kinase and PPARgamma pathways, thereby increasing beta-oxidation of lipids, leading to decreased TG content, which ameliorated muscle insulin resistance. In the liver, adiponectin also activated AMPK, thereby downregulating PEPCK and G6Pase, leading to decreased glucose output from the liver. In conclusion, PPARgamma plays a central role in the regulation of adipocyte hypertrophy and insulin sensitivity. The upregulation of the adiponectin pathway by PPARgamma may play a role in the increased insulin sensitivity of heterozygous PPARgamma knockout mice, and activation of adiponectin pathway may provide novel therapeutic strategies for obesity-linked disorders such as type 2 diabetes and metabolic syndrome.
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PMID:[The mechanisms by which PPARgamma and adiponectin regulate glucose and lipid metabolism]. 1450 Nov 64

Adiponectin is a recently identified, insulin-sensitizing and anti-inflammatory protein released by adipocytes, which is paradoxically reduced in obesity. It suppresses endothelial activation. Physiological insulin resistance occurs in normal pregnancy and is exaggerated in women with preeclampsia (PE), together with enhanced inflammatory and endothelial activation. Women with increased body mass index (BMI) and insulin resistance are predisposed to PE. We hypothesized that adiponectin concentrations are reduced in normal pregnancy compared with postpartum values and further reduced in women with PE. Fifteen women with PE and 30 control subjects with similar first trimester BMI had adiponectin concentrations measured in the third trimester; postpartum measurements were repeated in 16 control subjects. Adiponectin concentration in healthy pregnant women correlated inversely with early pregnancy BMI (r=-0.47, P=0.01) and fasting insulin concentrations (r=-0.58, P=0.001). However, adiponectin concentrations did not differ significantly in pregnancy and postpartum samples (mean change, -0.15 microg/mL; 95% CI, -2.28 to 1.98, P=0.88). Plasma adiponectin concentrations were markedly elevated (P=0.01) in women with PE (mean, 21.6; SD, 8.18 microg/mL) compared with control subjects (mean, 14.7; SD, 7.06 microg/mL). Moreover, in PE, adiponectin concentrations did not correlate with first trimester BMI or insulin or with serum urate or creatinine concentrations or urinary protein levels. We conclude that plasma adiponectin concentrations are not elevated in normal human pregnancy and paradoxically elevated (by 47%) in women with PE. This may be secondary to exaggerated nonspecific adipocyte lipolysis or as a physiological response to enhance fat utilization and attenuate endothelial damage. Future studies should determine whether adiponectin concentrations help improve prediction of PE.
Hypertension 2003 Nov
PMID:Paradoxical elevation in adiponectin concentrations in women with preeclampsia. 1475 83

Adiponectin is a recently discovered hormone secreted by adipocytes that has been reported to enhance insulin sensitivity. Although insulin resistance and/or compensatory hyperinsulinemia are considered to be involved with hypertension in obese humans, the relationship between plasma adiponectin level and obesity-related hypertension has not been fully clarified. In this study, we investigated the effect of dietary conjugated linoleic acid (CLA), reported as an insulin sensitizer, on plasma adiponectin, plasma insulin, and blood pressure in Zucker diabetic fatty (ZDF) rats. During the onset of obesity, blood pressure increased in ZDF rats. The increase, however, was prevented by dietary CLA. After 8 weeks, accumulated plasma insulin and glucose were also attenuated by CLA feeding. Dietary CLA increased plasma adiponectin levels in ZDF rats and the increase was attributed to the enhanced mRNA expression in white adipose tissue. This study provides the first evidence that dietary CLA increases plasma adiponectin level through the enhancement of mRNA expression. We speculate that the increase alleviates hyperinsulinemia and prevents the onset of hypertension in CLA-fed ZDF rats.
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PMID:Conjugated linoleic acid enhances plasma adiponectin level and alleviates hyperinsulinemia and hypertension in Zucker diabetic fatty (fa/fa) rats. 1452 47

Normal metabolic balance is maintained by a complex homeostatic system involving multiple tissues and organs. Acquired or inherited defects associated to environmental factors in any part of this system can lead to metabolic disorders such as the syndrome X which is presently a frequent syndrome in industrialized countries. It is characterized by a cluster of risk factors of atherosclerosis including insulin resistance, hyperinsulinemia, impaired glucose tolerance or type 2 diabetes, hypertension, dyslipidemia, and coagulation abnormalities. Its pathophysiology is likely to involve insulin resistance at the level of both skeletal muscle and visceral adipose tissue and altered fluxes of metabolic substrates between these tissues that in turn impair liver metabolism. Therapeutic intervention favours at present diet and exercise prescriptions. In addition, if necessary, specific treatment of the metabolic disorders is required. In the treatment of insulin resistance, new promising drugs are likely to be used in the next future. In this regard, adipose tissue, once thought to function primarily as a passive depot for the storage of excess lipid, is now understood to play a much more active role in metabolic regulation, secreting a variety of metabolic hormones and actively functioning to prevent deleterious lipid accumulation in other tissues and to modulate the insulin resistance. Here, we review new advances in our understanding of mechanisms leading to insulin resistance and type 2 diabetes from the perspective of the role and interactions of recently identified adipocyte-specific chemical messengers, the adipocytokines, such as adiponectin, tumor necrosis factor-alpha, interleukin 6, and resistin.
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PMID:[Adipocytokins, obesity and development of type 2 diabetes]. 1459 11

Insulin resistance is one of the major risk factors associated with development of hypertension and atherosclerosis. Recent studies have shown that adiponectin, an adipocyte-derived hormone, may be involved in insulin resistance and development of atherosclerosis in diabetes patients. The aim of this study was to examine adiponectin levels in patients with essential hypertension to determine the relationships between adiponectin levels and insulin sensitivity and to examine the relationship of adiponectin with pulse wave velocity (PWV) in a general population based on the results of an epidemiological survey in Japan. In a clinical study, 20 normotensives (NT) and 30 non-treated essential hypertensives (EHT) were hospitalized, and euglycemic hyperinsulinemic glucose clamp (GC) was performed to evaluate insulin sensitivity defined as M value. EHT were divided into insulin-resistant EHT (EHT-R) and insulin-nonresistant EHT (EHT-N) according to the mean -1 SD of the M value of NT as a cut-off point. Fasting plasma glucose (FPG), immunoreactive insulin (IRI), and adiponectin concentrations were measured. There were no significant differences in body mass index (BMI) or FPG among the NT, EHT-N, and EHT-R groups. The M value and adiponectin concentration in EHT-R were significantly lower than those in the NT or EHT-N. The IRI level in the EHT-R was significantly higher than those in the other groups. A positive correlation between adiponectin concentration and M value was found in all subjects, and adiponectin concentration and M value were found to be significant determinants of each other in multiple regression analysis. In an epidemiological study, we studied 391 male inhabitants of rural communities in Hokkaido, Japan. Systolic blood pressure (SBP), BMI, FPG, IRI, and adiponectin were measured in all subjects early in the morning. Homeostasis model assessment (HOMA) values were calculated as an index of insulin sensitivity, and PWV was used as an index of atherosclerosis. A negative correlation between HOMA values and adiponectin concentration was found in all of the subjects. Multiple regression analysis revealed that adiponectin was a significant determinant for PWV in subjects less than 70 years of age. The results of the clinical study indicate that EHT-R had not only hyperinsulinemia but also a low concentration of adiponectin. The results of multiple regression analysis for determinants of degree of PWV using data obtained in the epidemiological study suggest that adiponectin plays a role in antiatherosclerosis, partly through improvement of insulin resistance.
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PMID:Role of adiponectin in insulin-resistant hypertension and atherosclerosis. 1462 Sep 25

Chronic inflammation is very common in patients on maintenance dialysis. It is associated with an increase of many cytokines (especially: IL-1, IL-6 and TNF alpha). This inflammation leads to hormonal dysregulation (leptin, adiponectin, insulin). Increase in cytokines is associated with a high cardio-vascular morbi-mortality for general population as well as for uremic patients. Many metabolic abnormalities are due to chronic inflammation: protein catabolism, anorexia and many others. Among them, the "metabolic" syndrome includes adiposis, dyslipemia, insulinoresistance and high blood pressure very often present in chronic uremic patients. It is still unknown whether anti-inflammatory treatments would improve inflammation consequences in dialysis.
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PMID:[Metabolic consequences of inflammation in kidney failure]. 1465 Jul 51

Peroxisome proliferator-activated receptor-gamma (PPARgamma), an orphan nuclear receptor, mediates adipocyte differentiation and is the cellular target for the thiazolidinedione group of insulin-sensitizing antidiabetic agents. We screened this receptor gene in a cohort of subjects with severe insulin resistance and have identified heterozygous missense mutations in several individuals from three families. Functional studies indicate that the receptor mutants are transcriptionally impaired and inhibit wild type PPARgamma action in a dominant-negative manner. The clinical phenotype of patients includes partial lipodystrophy, early-onset hypertension, dyslipidaemia and hepatic steatosis. Factors which contribute to the severe insulin resistance in affected individuals include diminished body fat mass, impaired lipid flux in adipose tissue and reduced circulating levels of adiponectin. In a large kindred of five individuals with severe insulin resistance, we have identified frameshift/premature stop mutations in PPARGAMMA; and the muscle-specific regulatory subunit of protein phosphatase 1 (PPP1R3A). The frameshift PPARgamma mutant exhibits complete loss of function with no dominant-negative activity; the PPP1R3A truncation mutant is mislocalized intracellularly. Individuals harbouring either gene defect alone have normal circulating insulin levels, but a combination of both genetic abnormalities co-segregates with severe insulin resistance.
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PMID:Peroxisome proliferator-activated receptor-gamma and insulin action: insights from human genetics. 1467 97

The prevalence of overweight and obesity continues to increase rapidly in the United States, with more than half of all adults currently overweight or obese. In general, people become obese because of a combination of inherited genes and a lifestyle consisting of low levels of physical activity and consumption of excess calories. Obesity, especially the central or visceral type, is a predisposing factor for the development of type 2 diabetes mellitus, hypertension, and cardiovascular disease (CVD). Obesity and type 2 diabetes are associated with insulin resistance. The relation among obesity, insulin resistance, and CVD appears to develop at a relatively young age. Central obesity is linked with hyperinsulinemia, insulin resistance, dyslipidemia, and proinflammatory and prothrombotic clinical states. Adipose tissue synthesizes and secretes biologically active molecules that may affect CVD risk factors. These chemical messengers include adiponectin, resistin, leptin, plasminogen activator inhibitor-1, tumor necrosis factor-alpha, and interleukin-6. In overweight and obese individuals, weight loss may improve insulin sensitivity, leading to reduction in risk factors for CVD and, consequently, the potential for cardiovascular events. Agents that improve insulin sensitivity, such as the thiazolidinediones, have been shown to reduce visceral obesity. Decreases in visceral adipose tissue contribute to improvements in insulin sensitivity and blood pressure, and weight loss reduces serum levels of triglycerides and low-density lipoprotein cholesterol while increasing serum levels of high-density lipoprotein cholesterol. Reduction of risk factors suggests that the development of cardiovascular disease will be reduced by the improvement of insulin sensitivity and weight loss.
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PMID:Obesity as a cardiovascular risk factor. 1467 64

Pathways leading from obesity to the manifestations of metabolic syndrome involve a number of metabolic risk factors, as well as adipokines, mediators of inflammatory response, thrombogenic and thrombolytic parameters, and vascular endothelial reactivity. Increased adipose tissue mass contributes to augmented secretion of proinflammatory adipokines, particularly tumor necrosis factor-alpha (TNF alpha), along with diminished secretion of the "protective" adiponectin. In our view, TNF alpha and adiponectin are antagonistic in stimulating nuclear transcription factor-kappa B (NF-kappa B) activation. Through this activation, TNF alpha induces oxidative stress, which exacerbates pathological processes leading to oxidized low-density lipoprotein and dyslipidemia, glucose intolerance, insulin resistance, hypertension, endothelial dysfunction, and atherogenesis. NF-kappa B activation further stimulates the formation of additional inflammatory cytokines, along with adhesion molecules which promote endothelial dysfunction. Elevated free fatty acid, glucose, and insulin levels enhance this NF-kappa B activation and further downstream modulate specific clinical manifestations of metabolic syndrome.
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PMID:A novel pathway to the manifestations of metabolic syndrome. 1498 Dec 9

The global burden of coronary heart disease (CHD) has led to the introduction of international guidelines to minimize the morbidity and mortality that result from this condition. These guidelines recognize the contribution of multiple risk factors to the development of CHD and advocate a multifaceted approach to treatment. Obesity, particularly visceral adiposity, contributes to the clustering of many other risk factors, such as hypertension, insulin resistance/type 2 diabetes and dyslipidemia, within individual patients. The molecular mechanisms underlying the metabolic abnormalities induced by visceral adiposity have yet to be fully elucidated; however, adipocytokines such as adiponectin, tumor necrosis factor-alpha and resistin seem to play an important role in this process. Obesity is a major modifiable CHD risk factor, and the benefits of weight loss are numerous, leading to improvements in several co-morbidities. Guidelines advocate lifestyle changes to correct excess bodyweight and improve the CHD risk factor profile. In addition, pharmacologic therapy is recommended for the management of other risk factors, such as hypertension and dyslipidemia, which may not be adequately controlled by lifestyle changes alone. Lowering low-density lipoprotein cholesterol (LDL-C) levels is the primary target for drug therapy for CHD prevention, and statins are first-line lipid-modifying therapy. The introduction of more efficacious statins with favorable effects on the lipid profile will optimize the control of dyslipidemia. Combining these new treatments with lifestyle changes and drug therapies for managing other CHD risk factors, as part of a multifaceted approach to treatment, will have benefits for CHD prevention.
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PMID:Obesity as the core of the metabolic syndrome and the management of coronary heart disease. 1502 38


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