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

Clinical and experimental data obtained in the last few years have modified the concept of adipose tissue as one solely directed at energy storage and release. The adipose tissue is a target organ for glucocorticoids and several studies have been carried out on the function of hypothalamic-pituitary-adrenal axis in obese subjects without conclusive results. A recent and innovative finding is that adipose tissue can produce cortisol from its inactive precursor, cortisone. The identification of leptin, a hormone synthesised by fat tissue, has ushered in the modern view of this tissue as a true endocrine organ. Leptin is produced primarily by subcutaneous and to a lesser extent by visceral adipose tissue, and has a central role in controlling body weight and, especially in regulating fat stores. Leptin is also involved in several complex functions, including physiological processes associated with puberty. Another hormone of fat tissue is angiotensinogen, which is produced in larger amounts by visceral than subcutaneous fat. Human and animals adipose tissue express a whole renin-angiotensin system (RAS). Angiotensin II, the final effector of this system is probably produced locally by adipose tissue. The function of adipose RAS is not well known. RAS can participate together with other hormones and substances, in adipocyte differentiation and fat tissue growth, but could be also involved in the pathogenesis of complications of obesity including arterial hypertension.
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PMID:Adipose tissue as an endocrine organ? A review of recent data related to cardiovascular complications of endocrine dysfunctions. 1519 92

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.
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PMID:The adipose tissue as a source of vasoactive factors. 1532 Jul 86

The renin-angiotensin-aldosterone system has been causally implicated in obesity-associated hypertension. We studied the influence of obesity and weight reduction on the circulating and adipose tissue renin-angiotensin-aldosterone system in menopausal women. Blood samples were analyzed for angiotensinogen, renin, aldosterone, angiotensin-converting enzyme activity, and angiotensin II. In adipose tissue biopsy samples, we analyzed angiotensinogen, renin, renin-receptor, angiotensin-converting enzyme, and angiotensin II type-1 receptor gene expression. Obese women (n=19) had higher circulating angiotensinogen, renin, aldosterone, and angiotensin-converting enzyme than lean women (n=19), and lower angiotensinogen gene expression in adipose tissue. Seventeen women successfully participated in a weight reduction protocol over 13 weeks to reduce daily caloric intake by 600 kcal. Body weight was reduced by -5%, as were angiotensinogen levels by -27%, renin by -43%, aldosterone by -31%, angiotensin-converting enzyme activity by -12%, and angiotensinogen expression by -20% in adipose tissue (all P<0.05). The plasma angiotensinogen decrease was highly correlated with the waist circumference decline (r=0.74; P<0.001). Weight and renin-angiotensin-aldosterone system reductions were accompanied by a -7-mm Hg reduced systolic ambulatory blood pressure. These data suggest that a 5% reduction in body weight can lead to a meaningfully reduced renin-angiotensin-aldosterone system in plasma and adipose tissue, which may contribute to the reduced blood pressure.
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PMID:Weight loss and the renin-angiotensin-aldosterone system. 1563 41

The renin-angiotensin system plays a critical role in the pathogenesis of obesity, obesity-associated hypertension, and insulin resistance. However, the biological actions of angiotensin II (AII) on insulin sensitivity remain controversial. Because angiotensinogen and AII receptors are expressed on adipose tissue, we investigated the effect of AII on the insulin sensitivity of isolated rat adipocytes. The results of a receptor binding assay showed the maximal AII binding capacity of adipocytes to be 8.3 +/- 0.9 fmol/7 x 10(6) cells and the dissociation constant to be 2.72 +/- 0.11 nM. Substantial expression of both type 1 and 2 AII (AT1 and AT2) receptors was detected by RT-PCR. AII had no effect on basal glucose uptake, but significantly potentiated insulin-stimulated glucose uptake; this effect was abolished by the AT1 antagonist, losartan. In addition, AII did not alter the insulin binding capacity of adipocytes, but increased insulin-stimulated tyrosine phosphorylation of the insulin receptor beta-subunit, Akt phosphorylation, and translocation of glucose transporter 4 to the plasma membrane. AII potentiated insulin-stimulated glucose uptake through the AT1 receptor and by alteration of the intracellular signaling of insulin. Intraperitoneal injection of Sprague Dawley rats with AII increased insulin sensitivity in vivo. In conclusion, we have shown that AII enhances insulin sensitivity both in vitro and in vivo, suggesting that dysregulation of the insulin-sensitizing effect of AII may be involved in the development of insulin resistance.
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PMID:Angiotensin II enhances insulin sensitivity in vitro and in vivo. 1570 82

Components of the adipose renin-angiotensin system (RAS) have been suggested as providing a potential path-way linking obesity to hypertension. In adipose cells, the biological responses to beta-adrenergic stimulation are mediated by an increase in intracellular cAMP. Because an association exists among body fat mass, hypertension, and increased sympathetic stimulation, we examined the influence of cAMP on angiotensinogen (ATG) expression and secretion in human adipose tissue and in parallel we studied the DNA binding activity of CRE transcriptional factors. A 24 h exposure to the cAMP analog 8Br-cAMP resulted in significant increases in ATG mRNA levels (+176+/-60%) and protein secretion (+40+/-27%). The ability of 8Br-cAMP to promote ATG gene expression was unaltered by H89, a protein kinase A inhibitor, because H89 per se was found to stimulate ATG mRNA levels and protein secretion. Moreover, 8Br-cAMP stimulated the specific CRE DNA binding activity (+115+/-14%) in human adipocyte nuclear extracts as assessed by electrophoretic mobility shift assays. These results indicate that cAMP upregulates in vitro ATG expression and secretion in human adipose tissue and that the induction in ATG mRNA levels appears to result, at least in part, from positive effects on the DNA binding activity of CRE transcription factors. Further studies are required to determine whether this regulatory pathway is activated in human obesity and to elucidate the importance of adipose ATG to the elevated blood pressure observed in this pathological state.
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PMID:Human adipose angiotensinogen gene expression and secretion are stimulated by cyclic AMP via increased DNA cyclic AMP responsive element binding activity. 1571 Oct 21

Obesity and its associated disorders are increasing in companion animals, particularly in dogs. We have investigated whether genes encoding key adipokines, some of which are implicated in the pathologies linked to obesity, are expressed in canine adipose tissues. Using RT-PCR, mRNAs encoding the following adipokines were detected in dog white adipose tissue: adiponectin, leptin, angiotensinogen, plasminogen activator inhibitor-1, IL-6, haptoglobin, metallothionein-1 and 2, and nerve growth factor. The adipokine mRNAs were present in all fat depots examined. Fractionation of adipose tissue by collagenase digestion showed that each gene was expressed in mature adipocytes. The mRNA for TNFalpha was not evident in adipose tissue, but was detected in isolated adipocytes. Fibroblastic preadipocytes from gonadal white fat were differentiated into adipocytes in primary culture and adipokine expression examined before and after differentiation (days 0 and 11, respectively). Each adipokine gene expressed in dog white adipocytes was also expressed in the differentiated cells. These results demonstrate that dog white adipose tissue expresses major adipokine genes, expression being in the adipocytes. Investigation of adipokine production and function will provide insight into the mechanisms involved in obesity-related pathologies in dogs and serve as a model for the related human diseases.
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PMID:Adipokine gene expression in dog adipose tissues and dog white adipocytes differentiated in primary culture. 1613 59

Obesity is associated with hypertension and other cardiovascular diseases especially in the African-American population. Human angiotensinogen (AGT) gene has seven single nucleotide polymorphisms (SNPs) in 1.2 kb region of its promoter. Recent studies have shown that variant -217A is associated with hypertension in African-American and Chinese population. Nucleotide sequence of the hAGT gene has shown that variant -217A almost always occurs with variants -532T, -793A and -1074T (forming haplotype AAT) and variant -217G almost always occurs with variants -532C, -793G and -1074G (forming haplotype GGG). Since hAGT gene is expressed in the adipose tissue and its expression in this tissue may play a role in hypertension, we have analyzed the role of haplotypes AAT and GGG on the expression of this gene in adipocytes. We show here that a reporter construct with haplotype AAT of the hAGT gene has increased promoter activity on transient transfection in pre-adipocytes and differentiated adipocytes as compared to the reporter construct containing GCGG haplotype. Increased expression of the AGT gene containing haplotype AAT in the liver and adipocytes may be a contributing factor for hypertension.
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PMID:A haplotype of angiotensinogen gene that is associated with essential hypertension increases its promoter activity in adipocytes. 1630 36

Adipokines or adipocytokines are the proteins secreted by the adipose tissue. These bioactive molecules include proteins that modify insulin sensitivity (acylation-stimulating protein (ASP), TNF-alpha IL-6, resistin, leptin and adiponectin), and proteins that have known effects on vascularity (angiotensinogen and the plasminogen inhibitor protein PAI-I). Several studies have found a close relationship between adipocytes and immune cells as a consequence of evolutionary mechanisms that favor metabolic adaptation and survival under adverse conditions. It is known that adipokines contribute to the inflammation and insulin resistance present in obese individuals. The aim of this review is to analyze current information related to the physiology of the adipose tissue, with a special emphasis on the secretion of adipokines and their role in inflammation. We recommend that therapies addressing the treatment of obesity related disorders should focus on modifying the inflammatory process that originates in the adipose tissue.
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PMID:[Adipocitokines, adipose tissue and its relationship with immune system cells]. 1638 6

Numerous association studies have been performed to evaluate the relationship between the angiotensinogen gene and the essential hypertension, but their results are conflicting. The conflicting results may be explained by methodological reasons, particularly genetic differences in the population samples, phenotypic differences in the hypertensive populations analyzed, lack of appropriate control for other hypertension risk factors in some studies, or limited statistical power among many studies. Furthermore, hypertension is a public health issue of great relevance in Baleric Islands (Spain). For these reasons we performed an association study about the relationship between the M235T, T174M and G-6A diallelic polymorphisms of the angiotensinogen gene and hypertension in a population from Majorca (Balearic Islands), in which a considerable homogeneity with respect to ethnicity and environmental factors could be documented. This population was composed of 109 patients and 107 controls. Alleles of the angiotensinogen gene were determined by PCR and restriction site polymorphism analysis. The different genotypes were tested for association with dependent variables by univariate and multivariate logistic regression analysis. In the univariate analysis we found no evidence of association between the angiotensinogen gene genotypes and hypertension. This lack of association was independent of obesity, familial history of hypertension and diabetes for the genotypes of the polymorphisms M235T and G-6A; however, in the multivariate analysis the T174T174 genotype showed an almost significant positive association with hypertension [OR = 2.76 (95% confidence interval: 1.00-7.65, p = 0.05)]. The T174T174 genotype also showed a significant negative association with obesity [OR = 0.41 (95% confidence interval: 0.18-0.90, p = 0.03)] that remained after adjustment by sex, hypertension and diabetes [OR = 0.26 (95% confidence interval: 0.10-0.65, p = 0.004)]. Our results: a) are in contrast with the results from most previous studies that found a relationship of the T174M polymorphism with hypertension, as in those studies the M174 allele was responsible for the association; b) emphasize the need for rigorous control for obsesity in the studies of association between the angiotensinogen gene and hypertension; c) underscore the importance and the utility of using concrete populations to carry out studies on the genetic dissection of hypertension.
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PMID:[Angiotensinogen gene T174M polymorphism: opposite relationships with essential hypertension and obesity in a homogeneous population from Majorca (Baleric Islands, Spain)]. 1651 3

In the recent years we have begun to appreciate that adipose tissue is more than just a passive repository for excess energy. It is a highly active endocrine organ secreting a range of bioactive peptides with both local and distant action collectively called 'adipokines' or 'adipose tissue hormones'. They include leptin, adiponectin, resistin, acylation-stimulating protein (ASP), plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor alpha (TNFalpha), interleukin 6, and angiotensinogen. Some of these are specific fat-related hormones that are involved in regulating energy homeostasis, carbohydrate and lipid metabolism, vascular homeostasis and immune response. Moreover, the tissue is implicated in the metabolism of some steroid hormones. Disturbances in adipokine production may have potential repercussions in the pathophysiology of obesity, insulin resistance, and dyslipidemia. Reversal or alleviation of these changes seem to be a promising target for management of the mentioned disorders. The objective of this review is to summarise the most important aspects of biology, actions and regulation of these hormones with a special emphasis on the most recent literature.
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PMID:[Adipose tissue: a new endocrine organ]. 1654 30


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