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

White adipose tissue (WAT) stores energy in the form of triglycerides, whereas brown tissue (BAT) expends energy, primarily by oxidizing lipids. WAT also secretes many cytokines and acute-phase proteins that contribute to insulin resistance in obese subjects. In this study, we have investigated the mechanisms by which activation of peroxisome proliferator-activated receptor gamma (PPARgamma) with synthetic agonists induces a brown phenotype in white adipocytes in vivo and in vitro. We demonstrate that this phenotypic conversion is characterized by repression of a set of white fat genes ("visceral white"), including the resistin, angiotensinogen, and chemerin genes, in addition to induction of brown-specific genes, such as Ucp-1. Importantly, the level of expression of the "visceral white" genes is high in mesenteric and gonadal WAT depots but low in the subcutaneous WAT depot and in BAT. Mutation of critical amino acids within helix 7 of the ligand-binding domain of PPARgamma prevents inhibition of visceral white gene expression by the synthetic agonists and therefore shows a direct role for PPARgamma in the repression process. Inhibition of the white adipocyte genes also depends on the expression of C/EBPalpha and the corepressors, carboxy-terminal binding proteins 1 and 2 (CtBP1/2). The data further show that repression of resistin and angiotensinogen expression involves recruitment of CtBP1/2, directed by C/EBPalpha, to the minimal promoter of the corresponding genes in response to the PPARgamma ligand. Developing strategies to enhance the brown phenotype in white adipocytes while reducing secretion of stress-related cytokines from visceral WAT is a means to combat obesity-associated disorders.
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PMID:C/EBPalpha and the corepressors CtBP1 and CtBP2 regulate repression of select visceral white adipose genes during induction of the brown phenotype in white adipocytes by peroxisome proliferator-activated receptor gamma agonists. 1956 8

Recent studies indicate that obesity may play a key role in modulating genetic predispositions to type 2 diabetes (T2D). This study examines the main effects of both single-locus and multilocus interactions among genetic variants in Taiwanese obese and nonobese individuals to test the hypothesis that obesity-related genes may contribute to the etiology of T2D independently and/or through such complex interactions. We genotyped 11 single nucleotide polymorphisms for 10 obesity candidate genes including adrenergic beta-2-receptor surface, adrenergic beta-3-receptor surface, angiotensinogen, fat mass and obesity associated gene, guanine nucleotide binding protein beta polypeptide 3 (GNB3), interleukin 6 receptor, proprotein convertase subtilisin/kexin type 1 (PCSK1), uncoupling protein 1, uncoupling protein 2, and uncoupling protein 3. There were 389 patients diagnosed with T2D and 186 age- and sex-matched controls. Single-locus analyses showed significant main effects of the GNB3 and PCSK1 genes on the risk of T2D among the nonobese group (p = 0.002 and 0.047, respectively). Further, interactions involving GNB3 and PCSK1 were suggested among the nonobese population using the generalized multifactor dimensionality reduction method (p = 0.001). In addition, interactions among angiotensinogen, fat mass and obesity associated gene, GNB3, and uncoupling protein 3 genes were found in a significant four-locus generalized multifactor dimensionality reduction model among the obese population (p = 0.001). The results suggest that the single nucleotide polymorphisms from the obesity candidate genes may contribute to the risk of T2D independently and/or in an interactive manner according to the presence or absence of obesity.
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PMID:Gene-gene interactions among genetic variants from obesity candidate genes for nonobese and obese populations in type 2 diabetes. 1959 64

Circulating leptin is elevated in some forms of obesity-related hypertension, associated with impaired baroreflex function. Leptin receptors are present on vagal afferent fibers and neurons within the solitary tract nucleus, providing an anatomic distribution consistent with baroreflex modulation. Although solitary tract nucleus microinjection of 144 fmol/60 nL of leptin had no significant effect on baroreflex sensitivity for control of the heart rate in urethane/chloralose-anesthetized Sprague-Dawley rats, 500 fmol of leptin impaired baroreflex sensitivity for bradycardia in response to increases in pressure (1.15+/-0.04 versus 0.52+/-0.12 ms/mm Hg; P<0.01). Transgenic ASrAOGEN rats with low brain angiotensinogen have an upregulation of the leptin receptor and p85 alpha mRNA in the dorsal medulla relative to Sprague-Dawley rats. Consistent with these observations, the response to leptin was enhanced in ASrAOGEN rats, because both the 144-fmol (1.46+/-0.08 versus 0.75+/-0.10 ms/mm Hg; P<0.001) and 500-fmol (1.36+/-0.32 versus 0.44+/-0.06 ms/mm Hg; P<0.05) leptin microinjections impaired baroreflex sensitivity. At these doses, leptin microinjection had no effect on resting pressure, heart rate, or the tachycardic response to decreases in pressure in Sprague-Dawley or ASrAOGEN rats. Thus, exogenous leptin at sites within the solitary tract nucleus impairs the baroreflex sensitivity for bradycardia induced by increases in arterial pressure, consistent with a permissive role in mediating increases in arterial pressure. Baroreflex inhibition was enhanced in animals with evidence of increased leptin receptor and relevant signaling pathway mRNA.
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PMID:Leptin impairs cardiovagal baroreflex function at the level of the solitary tract nucleus. 1977 Apr 2

In addition to its role as an energy store, adipose tissue also acts as an endocrine organ, synthesizing and secreting hormones and cytokines. This review discusses angiotensin II (Ang-II), the biologically active component of the renin-angiotensin system (RAS). Evidence suggests that a functioning RAS is present in adipose tissue. Animal studies have demonstrated that modifying the amount of Ang-II in the body (eg, using RAS knockout/transgenic animal models or the pharmacological treatment of animal models to prevent the formation or action of Ang-II) directly influences body weight and adiposity. In humans, body fat is correlated with levels of angiotensinogen, a precursor of Ang-II. Thus, the treatment of obesity could be improved through the use of substances that interfere with Ang-II.
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PMID:Antagonists of the renin-angiotensin system and the prevention of obesity. 1977 95

Cardiovascular diseases are currently the most frequent cause of death in Poland and their incidence continually rises. This is related to the high incidence of obesity associated with insulin resistance, which is present in type 2 diabetes mellitus. Adipose tissue produces multiple cytokines(TNF-alpha, IL-6, PAI-1, CRP, angiotensinogen, leptin, adiponectin, visfatin, apelin, resistin)which decrease insulin sensitivity and induce inflammatory processes, endothelial dysfunction,and atherosclerosis. This article presents the link between obesity, insulin resistance, and type 2 diabetes mellitus according to studies conducted in vitro and in animal models. In human studies, the influence of resistin on the development of insulin resistance is controversial. The article underlines the role of resisitin in the development of inflammatory processes and endothelial dysfunction in humans. In clinical studies, resistin was shown to be a predictive factor of coronary artery disease and mortality connected with cardiovascular diseases.
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PMID:[Resistin: a pathogenic factor or a biomarker of metabolic disorders and inflammation?]. 1994 Mar 27

White adipose tissue (WAT) is an important endocrine organ that secretes approximately 30 biologically active peptides and proteins, collectively termed "adipokines". These are either produced exclusively by WAT (mainly adiponectin, leptin and resistin) or also by other tissues [e.g. tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, plasminogen activator inhibitor (PAI)-1, angiotensinogen]. Adipokines play a central role in body homeostasis including the regulation of food intake and energy balance, insulin action, lipid and glucose metabolism, angiogenesis and vascular remodelling, regulation of blood pressure and coagulation. Excess WAT, especially visceral obesity, is linked to obesity-related health problems through insulin resistance (IR) [leading to type 2 diabetes mellitus (T2DM)] and systemic low-grade inflammation [leading to cardiovascular disease (CVD)]. The adipokines are important mediators of these adverse effects. This review describes the role of proinflammatory adipokines in the pathogenesis of IR and of the chronic inflammatory state associated with visceral obesity. Moreover, it summarises treatment options for the normalisation of adipokine levels, which might confer an additional clinical benefit in the effort to prevent or treat obesity-related T2DM and CVD.
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PMID:Should adipokines be considered in the choice of the treatment of obesity-related health problems? 2001 25

Adipose tissue expresses all components of the renin-angiotensin system including angiotensinogen (AGT). Recent studies have highlighted a potential role of AGT in adipose tissue function and homeostasis. However, some controversies surround the regulatory mechanisms of AGT in obese adipose tissue. In this context, we here demonstrated that the AGT messenger RNA (mRNA) level in human subcutaneous adipose tissue was significantly reduced in obese subjects as compared with nonobese subjects. Adipose tissue AGT mRNA level in obese mice was also lower as compared with their lean littermates; however, the hepatic AGT mRNA level remained unchanged. When 3T3-L1 adipocytes were cultured for a long period, the adipocytes became hypertrophic with a marked increase in the production of reactive oxygen species. Expression and secretion of AGT continued to decrease during the course of adipocyte hypertrophy. Treatment of the 3T3-L1 and primary adipocytes with reactive oxygen species (hydrogen peroxide) or tumor necrosis factor alpha caused a significant decrease in the expression and secretion of AGT. On the other hand, treatment with the antioxidant N-acetyl cysteine suppressed the decrease in the expression and secretion of AGT in the hypertrophied 3T3-L1 adipocytes. Finally, treatment of obese db/db mice with N-acetyl cysteine augmented the expression of AGT in the adipose tissue, but not in the liver. The present study demonstrates for the first time that oxidative stress dysregulates AGT in obese adipose tissue, providing a novel insight into the adipose tissue-specific interaction between the regulation of AGT and oxidative stress in the pathophysiology of obesity.
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PMID:Adipose tissue-specific dysregulation of angiotensinogen by oxidative stress in obesity. 2004 38

The last two decades brings many data about white adipose tissue capacity to secrete hormones, named adipokines, which could mediate the relationship between obesity and lung diseases. In this paper we presented some data about adipokines involvement on pulmonary function, with special emphasis on leptin, adiponectin, tumor necrosis factor alpha, vascular endothelial growth factor, resistin, hepatocyte growth factor, interleukin-6, angiotensinogen and apelin.
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PMID:Adipokines involvement in lung function. 2020 Dec 59

Sucrose-fed rats, a model of metabolic syndrome, are characterized by insulin resistance, obesity, hypertension, and high plasma levels of triacylglycerols and angiotensin II (Ang II). However, whether tissue renin-angiotensin system (RAS) is altered in metabolic syndrome is unclear. To study this issue, food ad libitum and water (C) or 20% sucrose solution (SC) were given to adult male Wistar rats, for 30 days. Body weight (BW), blood pressure (BP), epididymal adipose tissue (EPI) mass, rate of in vivo fatty acid (FA) synthesis in EPI, circulating glucose, insulin, leptin, angiotensins I and II, triacylglycerols, and plasma renin (PRA) and angiotensin-converting enzyme (ACE) activities were evaluated. In kidneys and EPI, gene and protein expression of type 1 (AT(1)) and 2 (AT(2)) Ang II receptors, ACE, angiotensinogen (AGT) as well as protein expression of angiotensin-converting enzyme 2 (ACE2) were determined. In both tissues, Ang I, Ang II and Ang-(1-7) contents were also measured by HPLC. In SC rats higher BP, EPI mass, circulating triacylglycerols, insulin, leptin, PRA and, Ang II were found. In EPI, the rate of in vivo FA synthesis was associated with increased Ang-(1-7), protein expression of AT(1) and AT(2) receptors, ACE2, AGT, and gene expression of AGT although a reduction in ACE activity and in adipose Ang I and Ang II contents was observed. In kidneys, AT(1) and AT(2), ACE and AGT gene and protein expression as well as protein expression of ACE2 were unaltered while Ang II, Ang-(1-7) and ACE activity increased. These RAS component changes seem to be tissue specific and possibly are related to enhancement of FA synthesis, EPI mass and hypertension.
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PMID:High sucrose intake in rats is associated with increased ACE2 and angiotensin-(1-7) levels in the adipose tissue. 2034 75

The relationship between obesity and hypertension is well established both in children and adults. The mechanisms through which obesity directly causes hypertension are still an area of research. Activation of the sympathetic nervous system has been considered to have an important function in the pathogenesis of obesity-related hypertension. The arterial-pressure control mechanism of diuresis and natriuresis, according to the principle of infinite feedback gain, seems to be shifted toward higher blood-pressure levels in obese individuals. During the early phases of obesity, primary sodium retention exists as a result of increase in renal tubular reabsorption. Extracellular-fluid volume is expanded and the kidney-fluid apparatus is resetted to a hypertensive level, consistent with a model of hypertension because of volume overload. Plasma renin activity, angiotensinogen, angiotensin II and aldosterone values display significant increase during obesity. Insulin resistance and inflammation may promote an altered profile of vascular function and consequently hypertension. Leptin and other neuropeptides are possible links between obesity and the development of hypertension. Obesity should be considered as a chronic medical condition, which is likely to require long-term treatment. Understanding of the mechanisms associated with obesity-related hypertension is essential for successful treatment strategies.
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PMID:Mechanisms of obesity-induced hypertension. 2044 53


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