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

Angiotensin II, via activation of AT1 receptors in the kidney regulates sodium/fluid homeostasis and blood pressure. An exaggerated action of angiotensin II mediated via activation of AT1 receptors has been implicated in the increased renal sodium retention and the resetting of the pressure natriuresis in obesity related hypertension. Treatment of obese Zucker rats with AT1 receptor blockers reduces blood pressure to a greater extent and produces greater natriuresis. Also, there is an increased membranal AT1 receptor numbers and angiotensin II produces greater activation of sodium transporters in the isolated tubules from obese Zucker rats. Interestingly, AT2 receptors, which are believed to be beneficial to the renal and cardiovascular function in terms of their action on kidney and blood vessels, are greatly increased in proximal tubular membranes of obese Zucker rats. Whole animal and in vitro studies indicate that higher plasma insulin level, generally associated with obesity, is responsible for the up-regulation of both AT1 and AT2 receptors in the kidney. Determining the consequence of selective blocking of AT1 receptors and/or activation of the AT2 receptors on renal and cardiovascular function, and the effect of lowering insulin on these receptors present an important area of further investigation in obesity.
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PMID:Renal angiotensin II receptors, hyperinsulinemia, and obesity. 1459 64

Obesity has a high and rising prevalence and represents a major public health problem. Obstructive sleep apnea (OSA) is also common, affecting an estimated 15 million Americans, with a prevalence that is probably also rising as a consequence of increasing obesity. Epidemiologic data support a link between obesity and hypertension as well as between OSA and hypertension. For example, untreated OSA predisposes to an increased risk of new hypertension, and treatment of OSA lowers blood pressure, even during the daytime. Possible mechanisms whereby OSA may contribute to hypertension in obese individuals include sympathetic activation, hyperleptinemia, insulin resistance, elevated angiotensin II and aldosterone levels, oxidative and inflammatory stress, endothelial dysfunction, impaired baroreflex function, and perhaps by effects on renal function. The coexistence of OSA and obesity may have more widespread implications for cardiovascular control and dysfunction in obese individuals and may contribute to some of the clustering of abnormalities broadly defined as the metabolic syndrome. From the clinical and therapeutic perspectives, the presence of resistant hypertension and the absence of a nocturnal decrease in blood pressure in obese individuals should prompt the clinician to consider the diagnosis of OSA, especially if clinical symptoms suggestive of OSA (such as poor sleep quality, witnessed apnea, excessive daytime somnolence, and so forth) are also present.
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PMID:Obesity, sleep apnea, and hypertension. 1461 96

Obesity has become an epidemic problem in western societies, contributing to metabolic diseases, hypertension, and cardiovascular disease. Overweight and obesity are frequently associated with increased plasma levels of aldosterone. Recent evidence suggests that human fat is a highly active endocrine tissue. Therefore, we tested the hypothesis that adipocyte secretory products directly stimulate adrenocortical aldosterone secretion. Secretory products from isolated human adipocytes strongly stimulated steroidogenesis in human adrenocortical cells (NCI-H295R) with a predominant effect on mineralocorticoid secretion. Aldosterone secretion increased 7-fold during 24 h of incubation. This stimulation was comparable to maximal stimulation of these cells with forskolin (2 x 10(-5) M). On the molecular level, there was a 10-fold increase in the expression of steroid acute regulatory peptide mRNA. This effect was independent of adipose angiotensin II as revealed by the stimulatory effect of fat cell-conditioned medium even in the presence of the angiotensin type 1 receptor antagonist, valsartan. None of the recently defined adipocytokines accounted for the effect. Mineralocorticoid-stimulating activity was heat sensitive and could be blunted by heating fat cell-conditioned medium to 99 degrees C. Centrifugal filtration based on molecular mass revealed at least two releasing factors: a heat sensitive fraction (molecular mass >50 kDa) representing 60% of total activity, and an inactive fraction (molecular mass <50 kDa). However, the recovery rate increased to 92% when combining these two fractions, indicating the interaction of at least two factors. In conclusion, human adipocytes secrete potent mineralocorticoid-releasing factors, suggesting a direct link between obesity and hypertension.
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PMID:Human adipocytes secrete mineralocorticoid-releasing factors. 1461 37

Endothelial dysfunction is a critical factor in the development of vascular disease in patients with diabetes mellitus. Maintenance of the vascular tone and luminal diameter of a blood vessel is dependent on the net balance of vasoconstrictor and vasodilator forces. In both diabetes and obesity, vascular reactivity is abnormal. After ischemia, carbon dioxide challenge, thermal challenge, or exercise, individuals with diabetes do not exhibit the increase in blood flow or vasodilation observed in persons without diabetes. The mechanisms involved in abnormal reactivity may include both the endothelium and vascular smooth muscle. Major vasodilator factors that act on vascular smooth muscle cells are nitric oxide, prostacyclin, and hyperpolarizing factor. The main vasoconstrictors are endothelin, angiotensin II, norepinephrine, serotonin, and thromboxane A(2). In patients with diabetes, there is an increase in vasoconstrictors and a decrease in vasodilators. Thiazolidinediones (TZDs) improve vasodilative responses, which may be of importance in the treatment of vascular disease. The TZDs have anti-inflammatory effects and suppress free fatty acids and reactive oxygen species at the endothelial level, which may contribute to the improved vascular reactivity observed in patients treated with these agents. In addition, these effects of TZDs may have implications for reducing the incidence and severity of atherosclerosis in the long term.
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PMID:Vascular reactivity and thiazolidinediones. 1467 71

BACKGROUND AND THERAPY: The metabolic syndrome comprises a virulent and lethal group of atherosclerotic risk factors, including dyslipidemia, obesity, systemic hypertension and insulin resistance. The prevalence of the metabolic syndrome has continuously grown in industrialized and developing countries during the last decades, and affects tens of millions of people in Germany and Europe. Particularly prominent as a risk factor for the development of insulin resistance is central obesity, which is causally involved in the pathogenesis of insulin resistance in addition to genetic predisposition. The metabolic syndrome can easily be diagnosed in clinical practice (guidelines of the WHO and ATP III panel), and immediate treatment of the metabolic syndrome is mandatory because those patients are at increased risk to develop overt diabetes mellitus, coronary artery disease and stroke. The high risk for cardiovascular diseases is supported by findings that the risk for myocardial infarction in patients with insulin resistance is as high as the risk of patients after their first myocardial infarction. Intentional weight reduction reduces abdominal obesity and beneficially modulates all features of the metabolic syndrome, while the benefits of aerobic exercise training are discussed controversially. Thus, weight reduction causally undoes essential features of the metabolic syndrome, but effects are often not enduring. Therefore, the treatment of cardiovascular risk factors such as hypertension and dislipidemia is essential. Of note, antihypertensive treatment is more effective than tight glucose control to reduce cardiovascular events. Diuretics, ACE-inhibitors and angiotensin II type 1 receptor antagonists are suggested as first line therapeutics. However, at least two antihypertensives are usually necessary to achieve the suggested goals of blood pressure reduction. In conclusion, the prevalence of the metabolic syndrome is continuously growing. Due to its adverse impact on cardiovascular disease, early detection and aggressive treatment is mandatory to ensure longlasting benefits for affected patients.
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PMID:[Arterial hypertension and metabolic syndrome]. 1468 1

Systemic hypertension is a leading risk factor for cardiovascular disease among Blacks. Essential hypertension in this population is dominantly related to salt-sensitivity acting via various interactive mechanisms including volume changes, nitric oxide inactivation, angiotensin II and insulin resistance. Excess morbidity and mortality among Black hypertensives are related to twin problems of ignorance and poverty, late diagnosis, genetically determined racial biological factors and co-existing diabetes mellitus and obesity arising from "western" adopted affluent life-style. This paper reviews these peculiarities and their implications in the management of a Black Hypertensive.
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PMID:Systemic hypertension in blacks: an overview of current concepts of pathogenesis and management. 1469 55

Insulin resistance is a key metabolic defect in type 2 diabetes that is exacerbated by obesity, especially if the excess adiposity is located intra-abdominally/centrally. Insulin resistance underpins many metabolic abnormalities-collectively known as the insulin resistance syndrome-that accelerate the development of cardiovascular disease. Thiazolidinedione anti-diabetic agents improve glycaemic control by activating the nuclear receptor peroxisome proliferator activated receptor-gamma (PPARgamma). This receptor is highly expressed in adipose tissues. In insulin resistant fat depots, thiazolidinediones increase pre-adipocyte differentiation and oppose the actions of pro-inflammatory cytokines such as tumour necrosis factor-alpha. The metabolic consequences are enhanced insulin signalling, resulting in increased glucose uptake and lipid storage coupled with reduced release of free fatty acids (FFA) into the circulation. Metabolic effects of PPARgamma activation are depot specific-in people with type 2 diabetes central fat mass is reduced and subcutaneous depots are increased. Thiazolidinediones increase insulin sensitivity in liver and skeletal muscle as well as in fat, but they do not express high levels of PPARgamma, suggesting that improvement in insulin action is indirect. Reduced FFA availability from adipose tissues to liver and skeletal muscle is a pivotal component of the insulin-sensitising mechanism in these latter two tissues. Adipocytes secrete multiple proteins that may both regulate insulin signalling and impact on abnormalities of the insulin resistance syndrome--this may explain the link between central obesity and cardiovascular disease. Of these proteins, low plasma adiponectin is associated with insulin resistance and atherosclerosis--thiazolidinediones increase adipocyte adiponectin production. Like FFA, adiponectin is probably an important signalling molecule regulating insulin sensitivity in muscle and liver. Adipocyte production of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis, and angiotensin II secretion are partially corrected by PPARgamma activation. The favourable modification of adipocyte-derived cardiovascular risk factors by thiazolidinediones suggests that these agents may reduce cardiovascular disease as well as provide durable glycaemic control in type 2 diabetes.
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PMID:Central role of the adipocyte in the insulin-sensitising and cardiovascular risk modifying actions of the thiazolidinediones. 1473 74

Atherosclerosis is a complex, chronic disease state that usually arises from the converging action of several pathogenic processes, including hypertension, hyperlidemia, obesity and insulin resistance. Significantly, due to the increasing incidence of type 2 diabetes worldwide, several aspects of the renin-angiotensin system, including the capacity for angiotensin II synthesis and binding are increased in human and animal models of type II diabetes, and potentiate vascular lesion formation. Angiotensin II, an important vasoactive peptide of the renin-angiotensin system, profoundly accelerates atherosclerosis in animal models of diabetes. Conversely, in both human and animal studies, inhibition of angiotensin II synthesis or activity has been shown to significantly reduce atherosclerosis and cardiovascular mortality. Cardiovascular protection is independent of blood pressure and baseline activity of the renin-angiotensin system, suggesting an important and direct role for the vascular renin-angiotensin system in atherosclerotic progression. Angiotensin II appears to accelerate atherosclerosis through activation of several distinct signal transduction pathways, and via these mechanisms can function as a vascular growth and migration factor, a pro-inflammatory cytokine and an oxidative stress agent. Thiazolidinediones, a class of oral insulin-sensitizing agents in broad clinical use for the treatment of type 2 diabetes, have been shown to ameliorate cardiovascular disease in animal trials and clinical studies. Thiazolidinediones also appear to regulate angiotensin II signaling at multiple levels, significantly reducing the expression of the angiotensin II type 1 receptor and repressing signal transduction through this receptor to suppress vascular remodeling, lesion formation, and oxidative stress.
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PMID:Angiotensin II, PPAR-gamma and atherosclerosis. 1476 73

Thirst and appetite-mediated ingestive behavior develop and are likely programmed in utero, thus preparing for newborn and adult ingestive behavior. Fetal swallowing activity is markedly different from that of the adult, as spontaneous fetal swallowing occurs at a markedly (six-fold) higher rate compared with spontaneous adult drinking activity. This high rate of fetal swallowing is critical for the regulation of amniotic fluid volume and the development of the fetal gastrointestinal tract. Disordered fetal swallowing has been associated with both a decrease (oligohydramnios) and increase (polyhydramnios) in amniotic fluid volume. Both conditions are associated with a significant increase in perinatal morbidity and mortality, and limited treatment modalities are currently available. The mechanisms underlying the high rate of human fetal swallowing are regulated, in part, by tonic activity of central angiotensin II, glutamate N-methyl-D-aspartate receptors, and neuronal nitric oxide synthase. Fetal hypertonicity-mediated dipsogenesis is likely programmed in utero, as offspring of water-restricted ewes demonstrate a programmed syndrome of plasma hypertonicity, with significant hematologic and cardiovascular alterations. Similar to dipsogenic mechanisms, peripheral and central fetal orexic mechanisms also develop in utero, as demonstrated by increased fetal swallowing after both oral sucrose infusion and central injection of neuropeptide Y. The role of leptin in regulating fetal ingestive behavior is interesting because, contrary to actions in adults, leptin does not suppress fetal ingestive behavior. Teleologically, this may be of value during the newborn period, as unopposed appetite stimulatory mechanisms may facilitate rapid fetal and newborn weight gain. An adverse intrauterine environment, with altered fetal orexic factors during the critical developmental period of fetal life, may alter the normal setpoints of appetitive behavior and potentially lead to programming of adulthood hyperphagia and obesity. Further research is needed to delineate the mechanistic relationship between the intrauterine environment and the development of the setpoints of adult appetite and thirst.
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PMID:In utero development of fetal thirst and appetite: potential for programming. 1505 Oct 31

The disproportionate impact of cardiovascular disease in African Americans is well recognized. Not only do risk factors such as obesity occur at a higher rate in the African-American community, but this population experiences a greater mortality from cardiovascular disease than their white counterparts. The cardiovascular system is regulated in part by two opposing mediators linking the risk factors of obesity, vascular dysfunction, and diabetes. One of these mediators--angiotensin II--increases blood pressure, impairs endothelial function, decreases peroxisome proliferator activated-receptor gamma, and is proinflammatory, growth stimulating, profibrotic, and proatherogenic. The other mediator, peroxisome proliferator activated-receptor gamma, lowers blood pressure, improves endothelial function, decreases angiotensin II type 1 receptor function, and is anti-inflammatory, growth-inhibiting, antifibrotic, and antiatherogenic. Genotypic variants have been discovered that affect the functioning of both of these important systems. Some of these variants--like some genotypic variants discovered in the adrenergic system--occur with different frequencies in African Americans than in Americans of European descent and may help to explain racial/ethnic differences in susceptibility to cardiovascular disease and aspects of the response to treatment. Recognition of these genotypic differences may permit the development of therapies tailored to individual patients.
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PMID:Physiology, genetics, and cardiovascular disease: focus on African Americans. 1507 62


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