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)

Although traditional risk factors for cardiovascular disease are common in dialysis patients, they alone cannot explain the unacceptably high prevalence of vascular disease in this patient group. Much recent interest has therefore focused on the role of various nontraditional cardiovascular risk factors, such as inflammation, wasting, obesity, vascular calcification, and oxidative stress. In addition, genetic factors such as single nucleotide polymorphisms (SNPs) may significantly influence the immune response, the levels of inflammatory markers and body composition, as well as the prevalence of vascular calcification in this patient group. While genetic variations in the tumor necrosis factor (TNF)-alpha-308 and interleukin (IL)-10 -1082 SNPs seem to be consistently associated with adverse clinical outcome in end-stage renal disease (ESRD) patients, the results regarding genetic variations in the IL-6 gene have been conflicting. To elucidate the respective role of DNA polymorphisms in the IL-6 and C-reactive protein (CRP) genes, as well as genes that encode vascular calcification inhibitors (such as fetuin-A, matrix Gla protein, and osteoprotegerin), sufficiently powered studies are needed in which both the protein product and the specific phenotype are determined. In addition, polymorphisms in genes related to body composition may be excellent candidates for analysis in the ESRD population, since nutritional parameters are strongly associated with adverse events in these patients. It seems conceivable that in the future, prognostic or predictive multigene DNA assays (which allow a simultaneous and rapid assessment of multiple genetic variants) will provide nephrologists with a more precise approach for the identification of "high-risk" ESRD patients and the development of accurate individualized treatment strategies.
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PMID:Gene polymorphism association studies in dialysis: the nutrition-inflammation axis. 1607 56

alpha2-HS glycoprotein (AHSG), also known as fetuin-A, inhibits insulin receptor autophosphorylation and tyrosine kinase activity in vitro and in vivo. Earlier we have shown that fetuin-null (KO) mice demonstrate improved insulin sensitivity and resistance to diet-induced obesity. Since aging is associated with insulin resistance and impaired glucose handling, we tested the hypothesis that fetuin-null (KO) mice are resilient to changes in insulin sensitivity associated with aging. Aged (80-week-old) fetuin-null mice were leaner and demonstrated significantly lower body weights compared to age- and sex-matched wild-type (WT) littermates. Leanness in aged fetuin KO mice was accompanied by a significant increase in dark-onset energy expenditure, without marked alteration of respiratory quotient. In comparison to WT mice, fetuin KO mice demonstrated a lower fasting insulin resistance index, and significantly lower blood glucose and insulin levels, following a 4h fast. Interestingly, despite significantly decreased insulin levels during a glucose tolerance test, aged fetuin-null mice demonstrated a similar glucose excursion as WT mice, indicative of improved insulin sensitivity. Analysis of aldehyde-fuchsin stained pancreas from aged fetuin KO mice indicated no difference in islet beta-cell size or number. An insulin tolerance test confirmed the increased insulin sensitivity of aged fetuin KO mice. Further, compared to WT mice, aged fetuin-null mice demonstrated increased skeletal muscle and liver IR autophosphorylation and TK activity. Taken together, this study suggests that the absence of fetuin may contribute to the improvement of insulin sensitivity associated with aging.
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PMID:Fetuin-null mice are protected against obesity and insulin resistance associated with aging. 1701 19

Traditional risk factors such as hypertension, diabetes, dyslipidemia, obesity and metabolic syndrome, as well as additional nontraditional risk factors, can damage the kidney directly and by promoting intrarenal atherogenesis. Evidence indicates that increased oxidative stress and inflammation may mediate most of the effects of risk factors on the kidney. Clinical studies have demonstrated a relationship between oxidative stress and inflammatory biomarkers, and a few studies indicate an inverse correlation of oxidative stress biomarkers with estimated glomerular filtration rate (eGFR). Further, surrogate indexes of atherosclerosis such as intima-media thickness and aortic pulse wave velocity have been demonstrated to be related to plasma concentrations of markers of endothelial activation, inflammation and fibrosis in patients with different stages of chronic kidney disease (CKD). Moreover, plasma concentrations of high-sensitivity C-reactive protein have been shown to be increased and related to left ventricular mass in CKD individuals having left ventricular hypertrophy. In contrast, in these patients, decreases in fetuin-A plasma levels have been reported. Considering the complex background of the pathophysiological changes characterizing CKD patients, we can consider cardiovascular disease a multifactorial complication of CKD.
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PMID:Oxidative stress, inflammation and cardiovascular disease in chronic renal failure. 1844 11

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

Obesity is an established risk factor for cardiovascular disease (CVD), yet, the underlying mechanisms are only poorly understood. The adipose tissue produces a variety of hormones and cytokines and thereby actively participates in a network of biomarkers that may be relevant for the development of CVD. Such obesity biomarkers have a great potential to better characterize the obesity phenotype that may be relevant for the risk of CVD beyond anthropometric parameters. They may be used to support mechanistic studies, to help identify individuals at risk for CVD, and to evaluate the effect of preventive measures. The present article discusses the role of some of the most promising obesity biomarkers in cardiovascular epidemiology, including inflammatory markers, adiponectin, resistin, and fetuin-A. Importantly, some of these markers have been related to cardiovascular risk even after accounting for anthropometric parameters. Further, the potential ability to manipulate blood levels of some of these biomarkers through medication, diet and lifestyle make them attractive markers for cardiovascular risk. However, many open questions remain--especially with regard to the causal role of the factors as well as with regard to the extent of improvement in CVD prediction by these markers--before measurement of these biomarkers may be recommended on a public health level.
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PMID:Use of obesity biomarkers in cardiovascular epidemiology. 1977 14

Obesity is a risk factor for chronic kidney disease (CKD) and nonalcoholic fatty liver disease (NAFLD). Recent studies identify mechanisms common to both diseases linked through an interorgan communication orchestrated by fetuin-A and adiponectin. In liver and kidney, the energy sensor 5'-AMP activated protein kinase (AMPK) is pivotal to directing podocytes and hepatocytes to compensatory and potentially deleterious pathways, leading to inflammatory and profibrotic cascades culminating in end-organ damage. Regulation of these early upstream pathways may provide new therapeutic targets for these increasingly common sequelae of obesity.
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PMID:Mechanisms linking obesity, chronic kidney disease, and fatty liver disease: the roles of fetuin-A, adiponectin, and AMPK. 2015 May 38

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent causes of hepatic dysfunction and is highly correlated with components of the metabolic syndrome such as obesity, insulin resistance and type 2 diabetes. Among others, nutritional factors, physical inactivity, genetic variants and visceral obesity have been identified as risk parameters for NAFLD. The complex pathophysiology of fatty liver degeneration, however, and especially the interaction between hepatocytes and adipose tissue has not been completely elucidated. Furthermore, it is not entirely understood whether insulin resistance generates fatty liver disease or vice versa. Nevertheless, adipocytokines are likely to be involved in the pathogenesis of NAFLD since they are secreted not only from adipose tissue but also from the liver. For several adipocytokines such as leptin, adiponectin, tumor necrosis factor-alpha, retinol binding protein 4 (RBP4) or fetuin-A a crucial role in the development and progression of fatty liver disease has been suggested. It has been accepted that obesity is an independent risk factor for NAFLD. Dysregulation of adipocytokines may represent an important mechanism linking increased fat mass in obesity with the development of fatty liver disease. Here, we discuss the association of RBP4 and other recently discovered adipocytokines and their relation with NAFLD.
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PMID:Retinol-binding protein 4 and new adipocytokines in nonalcoholic fatty liver disease. 2037 Jun 70

Obesity epidemic is in rise in almost every industrialized country and continues to be a growing problem worldwide. In fact, obesity per se has been recognized as a chronic disease. Consequently, there has been a cascade of metabolic changes initiated by the markedly risen prevalence that contributes to the increased incidence of diabetes, hypertension, and cardiovascular disease. Moreover, obesity is also associated with an increased risk of chronic kidney disease (CKD). The majority of the studies indicate a direct relationship between body mass index (BMI) and CKD risk. Moreover, current evidence emphasized the fact that central obesity measurements, such as waist circumference, could be a better predictor of CKD progression and mortality than BMI. The detrimental effects of obesity on kidney outcome have been recognized in nondialysis-dependent (NDD)-CKD patients. However, survival in overweight or obese CKD patients undergoing maintenance hemodialysis is paradoxically opposed compared with the general population. This "reverse epidemiology," however, is valid mainly for the inflammated end-stage renal disease (ESRD) patients. In fact, renal transplant recipients with higher BMI have inferior patient and graft survival compared to patients with lower BMI. This review also provides perspectives concerning the mechanisms associated with obesity, such as the renin-angiotensin-aldosterone system (RAAS) activation, and the role of leptin, adiponectin, fetuin-A, and adipose tissue, as factors that contribute to the development of CKD. Prevention strategies for CKD patients are also discussed and should be considered by clinicians.
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PMID:The role of obesity in kidney disease: recent findings and potential mechanisms. 2154 51

Fetuin-A is a biomarker reported to be important in many metabolic disorders, including obesity, diabetes, and hepatic steatosis. Although it is well known that fetuin-A is increased in diabetes and nonalcoholic fatty liver disease (NAFLD), the levels of fetuin-A in diabetic patients with NAFLD are unknown. Furthermore, the regulation of fetuin-A expression is still obscure. In this study, a total of 180 age- and sex-matched subjects with normal glucose tolerance, NAFLD, newly diagnosed diabetes (NDD), and NDD with NAFLD were recruited. We found that the levels of fetuin-A were significantly increased in NDD with NAFLD as compared with NDD or NAFLD subjects. We further used HepG2 cells to investigate the regulation of fetuin-A. Treatment with endoplasmic reticulum (ER) stress activator, thapsigargin, increased the expression of fetuin-A mRNA and protein in a time- and dose-dependent manner. Pretreatment with ER stress inhibitor, 4-phenylbutyrate, reversed high glucose or palmitate-induced fetuin-A expression. Moreover, treatment with 4-phenylbutyrate in both streptozotocin-induced and high-fat diet-induced diabetic mice not only decreased hepatic fetuin-A levels but also improved hyperglycemia. Taken together, we found that fetuin-A levels were increased in diabetes patients with NAFLD. Moreover, ER stress induced by high glucose and palmitate increased the expression of fetuin-A and further contributed to the development of insulin resistance.
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PMID:Endoplasmic reticulum stress induces the expression of fetuin-A to develop insulin resistance. 2261 60

Although type 2 diabetes mellitus (DM) is a chronic metabolic disorder with multiple etiologies, obesity has been constantly linked with insulin resistance and manifestation of type 2 DM. In addition, obesity is associated with hypertension, dyslipidemia, and fatty liver disease and is regarded as a subclinical inflammatory condition characterized by release of pro-inflammatory mediators such as cytokines from adipose tissue. Both, type 2 DM and obesity are considered as major risks for developing micro- and macrovascular diseases. Recent studies showed that impaired circulating levels of fetuin-A, which is involved in propagating insulin resistance as well as circulating levels of angiopoietins, which are growth factors promoting angiogenesis, were observed in patients with obesity, metabolic syndrome, and type 2 DM. However, independent of type 2 DM and obesity, defective regulation of fetuin-A and angiopoietin are playing a critical role in predisposing to coronary and peripheral vascular diseases. Therefore, mechanisms linking type 2 DM and obesity with fetuin-A and angiopoietins seem to be complex and are in need of further exploration. In this review, we aimed to present a summary concerning associations of type 2 diabetes, obesity, and vascular diseases with circulating levels of angiopoietins and fetuin-A. Furthermore, we aimed to focus on roles of fetuin-A and angiopoietins and to highlight the most plausible mechanisms that might explain their associations with type 2 DM and obesity.
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PMID:Fetuin-A and angiopoietins in obesity and type 2 diabetes mellitus. 2282 Aug 93


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