Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lectins are a structurally diverse class of (glyco)proteins which bind mono- and oligosaccharides with high specificity and in a reversible way. For many years, the unique sugar binding properties of plant lectins have been exploited for the development of biochemical tools for glycoprotein isolation and characterisation, and the use of lectins as a glycoprofiling tool has became much more sophisticated with the advent of lectin microarrays, in which a panel of lectins are immobilized on a single chip for glycomic analysis. Among the numerous lectins studied so far, those from legumes represent the largest family. They can be present at relatively high amounts depending on genetic as well as environmental factors, and are accumulated especially in the seeds. For this reason, some lectins as the phytohemagglutinin from the common bean Phaseolus vulgaris constitute a possible risk, since consumption of raw or incorrectly processed beans has been shown to cause outbreaks of gastroenteritis, nausea and diarrhoea. On the other hand, for these anti-nutritional properties, bean extracts enriched in lectins or in lectin-related amylase inhibitors are also finding a growing use as active ingredients of "weight-blockers" in dietetic preparations for obesity treatment. Current methods to determine the lectin levels in foods are based on immunoenzymatic or toxicity tests, which are largely aspecific. Very recently, the availability of proteomic methodologies has allowed to start development and validation of sensitive and specific assays for detecting trace amounts of harmful lectins in either raw or processed foods. In this review, the main aspects of current and perspective applications of mass spectrometry and proteomic technologies to the structural characterisation of legumes are presented, with focus on issues related to detection, identification, and quantification of phytohemagglutinins relevant for their biochemical, immunological and toxicological aspects.
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PMID:Proteomic approaches to study structure, functions and toxicity of legume seeds lectins. Perspectives for the assessment of food quality and safety. 1921 48

Obesity-resistance in AHSG-knockout mice indicate an important role of alpha2-Heremans-Schmid glycoprotein/fetuin-A (AHSG) in the development of obesity. We studied whether genetic variation within AHSG affects whole-body adiposity and regional fat distribution in humans. We genotyped 321 subjects at increased risk for type 2 diabetes for five single nucleotide polymorphisms (SNP) rs2248690, rs4831, rs2070635, rs4917, and rs1071592. Body fat distribution and ectopic hepatic and intramyocellular lipids were assessed by magnetic resonance techniques. AHSG levels were determined by immunoturbidimetry. The five chosen SNPs covered 100% of common genetic variation (minor allele frequency >/=0.05) within AHSG (r (2)>/=0.8). All SNPs were significantly associated with AHSG levels (p<0.0001), except for rs4831 (p=0.9) after adjustment for gender, age, and body mass index (BMI). AHSG levels were associated with liver fat content (p=0.0160) and BMI (p=0.0247) after adjustment for gender and age. While rs2248690 was nominally associated with BMI in the dominant model (p=0.0432), none of the SNPs was associated with regional fat distribution. Common genetic variation within AHSG does not appear to influence regional body fat distribution, but may affect whole-body adiposity in humans.
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PMID:AHSG gene variation is not associated with regional body fat distribution--a magnetic resonance study. 1935 88

Plasma phospholipid transfer protein (PLTP) is a lipid transfer glycoprotein that binds to and transfers a number of amphipathic compounds. In earlier studies, the attention of the scientific community focused on the positive role of PLTP in high-density lipoprotein (HDL) metabolism. However, this potentially anti-atherogenic role of PLTP has been challenged recently by another picture: PLTP arose as a pro-atherogenic factor through its ability to increase the production of apolipoprotein B-containing lipoproteins, to decrease their antioxidative protection and to trigger inflammation. In humans, PLTP has mostly been studied in patients with cardiometabolic disorders. Both PLTP and related cholesteryl ester transfer protein (CETP) are secreted proteins, and adipose tissue is an important contributor to the systemic pools of these two proteins. Coincidently, high levels of PLTP and CETP have been found in the plasma of obese patients. PLTP activity and mass have been reported to be abnormally elevated in type 2 diabetes mellitus (T2DM) and insulin-resistant states, and this elevation is frequently associated with hypertriglyceridemia and obesity. This review article presents the state of knowledge on the implication of PLTP in lipoprotein metabolism, on its atherogenic potential, and the complexity of its implication in obesity, insulin resistance and T2DM.
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PMID:Plasma phospholipid transfer protein (PLTP): review of an emerging cardiometabolic risk factor. 1941 3

Macrophage infiltration into adipose tissue is a hallmark of obesity. We recently reported two phenotypically distinct subsets of adipose tissue macrophages (ATM) based on the surface expression of the glycoprotein F4/80 and responsiveness to treatment with a peroxisome proliferator-activated receptor (PPAR) gamma agonist. Hence, we hypothesized that F4/80(hi) and F4/80(lo) ATM differentially express PPAR gamma. This study phenotypically and functionally characterizes F4/80(hi) and F4/80(lo) ATM subsets during obesity. Changes in gene expression were also examined on sorted F4/80(lo) and F4/80(hi) ATM by quantitative real-time RT-PCR. We show that while F4/80(lo) macrophages predominate in adipose tissue of lean mice, obesity causes accumulation of both F4/80(lo) and F4/80(hi) ATM. Moreover, accumulation of F4/80(hi) ATM in adipose tissue is associated with impaired glucose tolerance. Phenotypically, F4/80(hi) ATM express greater amounts of CD11c, MHC II, CD49b, and CX3CR1 and produce more TNF-alpha, MCP-1, and IL-10 than F4/80(lo) ATM. Gene expression analyses of the sorted populations revealed that only the F4/80(lo) population produced IL-4, whereas the F4/80(hi) ATM expressed greater amounts of PPAR gamma, delta, CD36 and toll-like receptor-4. In addition, the deficiency of PPAR gamma in immune cells favors expression of M1 and impairs M2 macrophage marker expression in adipose tissue. Thus, PPAR gamma is differentially expressed in F4/80(hi) versus F4/80(low) ATM subsets and its deficiency favors a predominance of M1 markers in WAT.
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PMID:PPAR gamma is highly expressed in F4/80(hi) adipose tissue macrophages and dampens adipose-tissue inflammation. 1942 85

Profound loss of adipose and other tissues is a hallmark of cancer cachexia, a debilitating condition associated with increased morbidity and mortality. Fat loss cannot be attributable to reduced appetite alone as it precedes the onset of anorexia and is much more severe in experimental models of cachexia than in food restriction. Morphological examination has shown marked remodelling of adipose tissue in cancer cachexia. It is characterised by the tissue containing shrunken adipocytes with a major reduction in cell size and increased fibrosis in the tissue matrix. The ultrastructure of 'slimmed' adipocytes has revealed severe delipidation and modifications in cell membrane conformation. Although the molecular mechanisms remain to be established, evidence suggests that altered adipocyte metabolism may lead to adipose atrophy in cancer cachexia. Increased lipolysis appears to be a key factor underlying fat loss, while inhibition of adipocyte development and lipid deposition may also contribute. Both tumour and host-derived factors are implicated in adipose atrophy. Zinc-alpha2-glycoprotein (ZAG), which is overexpressed by certain malignant tumours, has been identified as a novel adipokine. ZAG transcripts and protein expression in adipose tissue are up regulated in cancer cachexia but reduced with adipose tissue expansion in obesity. Studies in vitro demonstrate that recombinant ZAG stimulates lipolysis. ZAG may therefore act locally, as well as systemically, to promote lipid mobilisation in cancer cachexia. Further elucidation of ZAG function in adipose tissue may lead to novel targets for preventing adipose atrophy in malignancy.
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PMID:New insights into adipose tissue atrophy in cancer cachexia. 1971 94

Apolipoprotein E is a polymorphic glycoprotein in humans with a molecular mass of 34.5 kDa. It is a component of chylomicron remnants, very low density lipoprotein, low density lipoprotein and high density lipoprotein, and is primarily responsible for maintaining plasma lipid homeostasis. In addition to these well-documented functions, recent studies in experimental mouse models, as well as population studies, show that apolipoprotein E also plays an important role in the development of obesity and insulin resistance. It is widely accepted that disruption in homeostasis between food intake and energy expenditure, and the subsequent deposition of excess fatty acids into fat cells in the form of triglycerides, leads to the development of obesity. Despite the pivotal role of obesity and dyslipidemia in the development of the metabolic syndrome and heart disease, the functional interactions between adipose tissue and components of the lipoprotein transport system have not yet been investigated thoroughly. In this minireview, we focus on the current literature pertinent to the involvement of apolipoprotein E in the development of pathologies associated with the metabolic syndrome.
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PMID:Mechanisms of obesity and related pathologies: role of apolipoprotein E in the development of obesity. 1975 75

The relative release in vitro of endothelin-1, zinc-alpha2-glycoprotein (ZAG), lipocalin-2, CD14, RANTES (regulated on activation, normal T cell expressed and secreted protein), lipoprotein lipase (LPL), osteoprotegerin (OPG), fatty acid-binding protein 4 (FABP-4), visfatin/PBEF/Nampt, glutathione peroxidase-3 (GPX-3), intracellular cell adhesion molecule 1 (ICAM-1), and amyloid A was examined using explants of human adipose tissue as well as the nonfat cell fractions and adipocytes from obese women. Over a 48-h incubation the majority of the release of LPL was by fat cells whereas that of lipocalin-2, RANTES, and ICAM-1 was by the nonfat cells present in human adipose tissue. In contrast appreciable amounts of OPG, amyloid A, ZAG, FABP-4, GPX-3, CD14, and visfatin/PBEF/Nampt were released by both fat cells and nonfat cells. There was an excellent correlation (r = 0.75) between the ratios of adipokine release by fat cells to nonfat cells over 48 h and the ratio of their mRNAs in fat cells to nonfat cells at the start of the incubation. The total release of ZAG, OPG, RANTES, and amyloid A by incubated adipose tissue explants from women with a fat mass of 65 kg was not different from that by women with a fat mass of 29 kg. In contrast that of ICAM-1, FABP-4, GPX-3, visfatin/PBEF/Nampt, CD14, lipocalin-2, LP, and endothelin-1 was significantly greater in tissue from women with a total fat mass of 65 kg.
Obesity (Silver Spring) 2010 May
PMID:Release of 12 adipokines by adipose tissue, nonfat cells, and fat cells from obese women. 1983 60

Zinc-alpha2-glycoprotein (ZAG, also listed as AZGP1 in the MGI Database), a lipid-mobilising factor, has recently been suggested as a potential candidate in the modulation of body weight. We investigated the effect of increased adiposity on ZAG expression in adipose tissue and the liver and on plasma levels in obese (ob/ob) mice compared with lean siblings. The study also examined the effect of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNFalpha) on ZAG expression in adipocytes. Zag mRNA levels were significantly reduced in subcutaneous (fourfold) and epididymal (eightfold) fat of ob/ob mice. Consistently, ZAG protein content was decreased in both fat depots of ob/ob mice. In the liver of obese animals, steatosis was accompanied by the fall of both Zag mRNA (twofold) and ZAG protein content (2.5-fold). Plasma ZAG levels were also decreased in obese mice. In addition, Zag mRNA was reduced in epididymal (fivefold) and retroperitoneal (fivefold) adipose tissue of obese (fa/fa) Zucker rats. In contrast to Zag expression, Tnfalpha mRNA levels were elevated in adipose tissue (twofold) and the liver (2.5-fold) of ob/ob mice. Treatment with TNFalpha reduced Zag gene expression in differentiated adipocytes, and this inhibition was chronic, occurring at 24 and 48 h following TNFalpha treatment. It is concluded that ZAG synthesis in adipose tissue and the liver is downregulated, as are its circulating levels, in ob/ob mice. The reduced ZAG production may advance the susceptibility to lipid accumulation in these tissues in obesity, and this could be at least in part attributable to the inhibitory effect of TNFalpha.
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PMID:Downregulation of zinc-{alpha}2-glycoprotein in adipose tissue and liver of obese ob/ob mice and by tumour necrosis factor-alpha in adipocytes. 1993 49

Although it has been reported that osteopontin, a matrix glycoprotein and proinflammatory cytokine, mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance, it remains unclear how osteopontin is up-regulated in adipose tissue in obese humans and animals. In this study, we incubated U937 mononuclear cells with adipocytes in a transwell system and studied how cell interaction regulated osteopontin expression. Results showed that coculture of U937 cells with adipocytes led to a marked increase in osteopontin production when compared with that released by independent cultures of U937 cells. Moreover, lipopolysaccharide or palmitic acid-induced TLR4 activation and high glucose further augmented the coculture-stimulated osteopontin secretion. Similar observations were made in the coculture of human primary monocytes and adipocytes. Real time PCR studies showed that coculture of U937 cells and adipocytes increased osteopontin mRNA in U937 cells, but not adipocytes, suggesting that adipocyte-derived soluble factor may stimulate osteopontin expression by U937 cells. In our studies to explore the underlying mechanism, we found that the neutralizing antibodies against interleukin (IL)-6 or IL-6 small interfering RNA transfection in adipocytes effectively inhibited coculture-stimulated osteopontin expression, suggesting that IL-6 released by adipocytes plays an essential role in the coculture-stimulated osteopontin expression by U937 cells. In conclusion, this study has demonstrated that cell interaction, TLR4 activation, and high glucose up-regulate osteopontin expression, and adipocyte-derived IL-6 played a major role in the up-regulation.
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PMID:Adipocyte-mononuclear cell interaction, Toll-like receptor 4 activation, and high glucose synergistically up-regulate osteopontin expression via an interleukin 6-mediated mechanism. 2000 8

Thrombophilia can be broadly defined as an increased tendency toward hypercoagulability and venous thrombosis. There are several defined risk factors for thrombosis, and these are generally distinguished as either acquired or congenital, although sometimes this distinction is blurred because of interrelationships. Congenital risk factors include deficiencies or defects in natural anticoagulants, such as antithrombin, Protein C and Protein S, and genetic polymorphisms such as prothrombin G20210A and cleavage-resistant forms of factor V (in particular factor V Leiden), that lead to a condition commonly known as activated protein C resistance. Acquired risk factors include antiphospholipid antibodies, detected as lupus anticoagulants and/or anticardiolipin antibodies and/or anti-beta-2-glycoprotein-I antibodies. High levels of clotting factors, dysfibrinogenemia, hyperhomocysteinemia, prolonged immobilization, increasing age, surgery, trauma, cancer, obesity, poor nutrition, pregnancy, oral contraceptives, and hormone replacement therapy comprise just some of the other risk factors. Each of these elements constitutes a component of increased risk, which is compounded when concomitant. There is ongoing debate regarding relative and compound risks, the value of laboratory screening, whom and when to screen for these markers, which tests and methodologies to use, and the form and duration of therapeutic management. The current article explores several important issues primarily from a scientific perspective and predominantly related to laboratory testing. Many of these issues appear to be simply overlooked by some clinicians managing patients with thromboses. In brief, although there is potential significance in testing for various thrombophilia-associated markers, this value is limited and greatly diminishes when inappropriately applied. The application of excessive or inappropriate thrombophilia testing is of particular concern, and the net effect of current worldwide testing trends is likely to be more detrimental than beneficial. In short, it is likely that current generalized testing is simply doing more harm than good, and thus that ordering practice requires scrutiny.
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PMID:Laboratory investigation of thrombophilia: the good, the bad, and the ugly. 2001 36


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