Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0948265 (metabolic syndrome)
24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adiponectin, the gene product of the adipose most abundant gene transcript 1, is a novel adipocyte-derived peptide that has been considered to have antiinflammatory and antiatherogenic effects. To characterize the relationship between adiponectin and lipids metabolism, we measured fasting plasma adiponectin concentration by ELISA, serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and apolipoprotein (apo) levels in 352 nondiabetic women, 16-86 yr old, with a wide range of body weight [body mass index (BMI), 14.8-36.3 kg/m(2)]. Plasma adiponectin concentrations in women with the highest tertile of TG (1.69 mM < or approximately) were decreased, compared with the middle (1.13 < or = approximately < 1.69) or lowest tertile of TG (approximately < 1.13) (5.9 +/- 0.5 vs. 7.5 +/- 0.3, 9.2 +/- 0.2 microg/ml; P < 0.005, 0.001). Plasma adiponectin with the lowest tertile of HDL-C (approximately < 1.16 mM) was decreased, compared with the middle (1.16 < or = approximately < 1.81) or highest tertile of HDL-C (1.81 < or approximately ) (5.7 +/- 0.5 vs. 7.8 +/- 0.2, 10.1 +/- 0.4 microg/ml; both P < 0.001). These relationships had similar tendencies after adjustment for BMI, body fat mass, age, or diastolic blood pressure. Adiponectin was negatively correlated with serum TG (r = -0.33, P < 0.0001), atherogenic index [(total cholesterol - HDL-C)/HDL-C] (r = -0.34, P < 0.0001), apo B (r = -0.45, P < 0.0001), or apo E (r = -0.29, P < 0.05), and positively correlated with serum HDL-C (r = 0.39, P < 0.0001) or apo A-I levels (r = 0.42, P < 0.002). Those negative relationships became stronger after adjusting for BMI or body fat mass. The slightly positive correlation between adiponectin and age, blood urea nitrogen, or creatinine levels was also observed (all P < 0.001). These results indicate that high-TGnemia and low-HDL-Cnemia are associated with low plasma adiponectin concentrations in nondiabetic women. Further efforts must now be targeted to determine whether adiponectin causes these lipid abnormalities and thus whether it is partly responsible for the atherogenic risk seen in the metabolic syndrome.
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PMID:Decreased plasma adiponectin concentrations in women with dyslipidemia. 1205 Feb 47

Adiponectin, also referred to as AdipoQ or ACRP30, is a plasma protein produced and secreted exclusively from adipose tissue. The protein contains a collagen-like domain and a C1q-like globular domain. A protease-generated globular segment enhances fatty acid oxidation in muscles, thereby modulating lipid and glucose metabolism. Plasma adiponectin levels are inversely correlated with the severity of insulin resistance. A recent genome-wide scan study mapped a susceptibility locus for type 2 diabetes and the metabolic syndrome to chromosome 3q27, where the adiponectin gene is located. Here, we screened Japanese patients with type 2 diabetes and age- and BMI-matched nondiabetic control subjects for mutations in adiponectin gene. We identified four missense mutations (R112C, I164T, R221S, and H241P) in the globular domain. Among these mutations, the frequency of I164T mutation was significantly higher in type 2 diabetic patients than in age- and BMI- matched control subjects (P < 0.01). Furthermore, plasma adiponectin concentrations of subjects carrying I164T mutation were lower than those of subjects without the mutation. All the subjects carrying I164T mutation showed some feature of metabolic syndrome, including hypertension, hyperlipidemia, diabetes, and atherosclerosis. Our findings suggest that I164T mutation is associated with low plasma adiponectin concentration and type 2 diabetes.
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PMID:Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome. 1208 69

In recent years, the simple paradigm of adipose tissue as merely a fat store is rapidly evolving into a complex paradigm of this tissue as multipotential secretory organ, partitioned into a few large depots, including visceral and subcutaneous location, and many small depots, associated with a variety of organs in the human body. The major secretory compartment of adipose tissue consists of adipocytes, fibroblasts, and mast cells. These cells, using endocrine, paracrine and autocrine pathways, secrete multiple bioactive molecules, conceptualized as adipokines or adipocytokines. This review examines current information in adipobiology of various diseases besides obesity and related diseases such as type 2 diabetes, metabolic syndrome, and cardiovascular disease. Finally, we emphasize the possibilities for adipokine-targeted pharmacology in adiponectin (Acrp30, apM1, AdipoQ, GBP28), angiotensin II, estrogens, nerve growth factor, tumor necrosis factor-alpha, and also adipose mast cells.
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PMID:Adipobiology of disease: adipokines and adipokine-targeted pharmacology. 1267 60

Adipose tissue is not simply a store of excess energy, but also secretes a variety of proteins into circulating blood that influence systemic metabolism. These include tumor necrosis factor (TNF-alpha), plasminogen activator inhibitor type 1 (PAI-1), leptin, resistine and adiponectin. These are collectively known as adipocytokines. Adiponectin (also referred to as AdipoQ, Acrp 30, apM1 or GBP28) is a novel adipose-specific protein. A recent genome study mapped a susceptibility locus for type 2 diabetes and the metabolic syndrome on chromosome 3q27, where the adiponectin gene is located. Adiponectin is a peculiar adipocytokine because in contrast to the markedly increased levels of many others, as leptin or TNF-alpha, its level is reduced in obesity and type 2 diabetes. The administration of thiazolidinediones, which are synthetic PPARs-gamma ligands, significantly increases the plasma adiponectin concentrations, an effect that could improve insulin sensitivity. Thus, the administration of adiponectin may provide a novel treatment modality for insulin resistance and type 2 diabetes.
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PMID:[Adiponectin: a new adipocytokine]. 1462 49

Adiponectin (also called AdipoQ, gelatin-binding protein 28, Acrp30) is a novel adipocytokine with important metabolic effects. It is physiologically released from adipose tissue and circulates in serum as a hexamer and larger multimeric structure of high molecular weight. Serum level of the protein correlates with systemic insulin sensitivity. Recently adiponectin receptors AdipoR1 and AdipoR2 have been discovered by expression cloning. AdipoR1 is abundantly expressed in skeletal muscles, whereas AdipoR2 is predominantly expressed in the liver. Marked expression of mRNA for AdipoR1 and AdipoR2 has been lately reported in pancreatic beta cells. Both of the receptors activate AMPK and PPAR alpha metabolic pathways leading to an increase in fatty acid oxidation, glucose uptake and a decreased rate of gluconeogenesis, thus enhancing insulin sensitivity. Moreover effects of adiponectin mimic many metabolic actions of insulin such as augmenting blood flow and glucose disposal in NO-dependent manner. The precise mechanism of regulation of plasma adiponectin level is unknown. Recently the mechanism of transcriptional activation of adiponectin gene via PPAR gamma was described. Its level seems to be decreased by TNFalfa and beta-adrenergic agonists. Furthermore there is increasing evidence that some genetic variants in the adiponectin gene may be associated with its ethnical differences in level as well as its likely clinical consequences. Hipoadiponectynemia is associated with obesity, metabolic syndrome, diabetes type 2, cardiovascular disease, lipodystrophy in AIDS. In patients with chronic renal failure, anorexia nervosa plasma adlponectin level is increased. Weight loss and therapy with thlazolidinediones are proved to enhance endogenous adlponectin production in humans. In summary, the ability of adiponectin to increase insulin sensitivity in conjunction with its anti-inflammatory and antiatherogenic properties have made this novel adipocytokine a promising therapeutic tool for the future, especially in individuals with low plasma levels of adiponectin.
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PMID:[Adiponectin--adipocytokine with a broad clinical spectrum]. 1523 Jan 53

This study aimed to determine whether polymorphisms of the adiponectin (ACDC) gene independently contribute to insulin resistance (IR) and other cardiovascular disease (CVD) risk factors in nonobese, nondiabetic Korean men after adjusting for major environmental factors that influence IR. Among the 7 ACDC single-nucleotide polymorphisms (SNPs;C-11377G, T45G, G276T, H241P, Y111H, G90S, and R221S) prescreened in 48 subjects, we genotyped 333 subjects for SNP45 and SNP276, both of which showed an allele frequency of more than 2%. In Pearson correlation and multiple stepwise regression analyses, we found that waist circumference was the most important influencing factor (beta = .369, P < .001) in homeostasis model assessment (HOMA)-IR, whereas plasma adiponectin was the second most important (beta = -.217, P = .023). At position 276, T/T subjects showed significantly lower glucose concentrations (P = .043) and higher low-density lipoprotein particle sizes (P = .033) than the G/G and G/T subjects. The subjects also had lower serum triglycerides and HOMA-IR; however, these results were not statistically significant. After adjusting for waist circumference and plasma adiponectin, T/T subjects showed a significantly lower HOMA-IR than G/G or G/T subjects (P = .048). On the other hand, at position 45, only glucose concentrations were significantly lower in G carriers (P = .005). In the SNP45-SNP276 haplotype test, TT/TT subjects (having T/T at both SNP45 and SNP276) showed significantly lower IR before and after adjusting for waist circumference and adiponectin levels than did other carriers. In conclusion, we suggest that SNP276G>T, rather than SNP45T>G, is more strongly associated (both directly and indirectly) than with several components of metabolic syndrome and CVD risk, including IR, triglyceride concentration, and low-density lipoprotein particle size, in nonobese, nondiabetic men.
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PMID:The SNP276G>T polymorphism in the adiponectin (ACDC) gene is more strongly associated with insulin resistance and cardiovascular disease risk than SNP45T>G in nonobese/nondiabetic Korean men independent of abdominal adiposity and circulating plasma adiponectin. 1632 20

Although already described five years ago, it is only from year 2000, following intensive research in the field of genetics that the adiponectin protein was related with insulin sensitivity, type 2 diabetes and the metabolic syndrome. The story began with a paradox as this protein exclusively secreted by fat tissue was dramatically decreased in patients presenting an excess of fat mass. Later this decrease was reported with insulin resistance and metabolic syndrome associated phenotypes. The search for genetic variants in the adiponectin encoding ACDC gene and epidemio genetic investigations allowed to associate genetic variations of the gene and phenotypic traits of the metabolic syndrome. One of the major points was the correlation of the levels of circulating adiponectin with insulin sensitivity, leading to a better knowledge of the role of adiponectin. Indeed it is now clearly admitted that adiponectin is an insulin sensitizing cytokine. Recently two adiponectin receptors were described and genetic variations in their genes were associated with features of the metabolic syndrome. Interactions of adiponectin with various partners are discussed in view of a better understanding of adiponectin resistance and insulin resistance.
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PMID:Adiponectin and its receptors: partners contributing to the "vicious circle" leading to the metabolic syndrome? 1667 33

To describe the function in terms of gene expression, and to find new factors, we performed random complementary DNA (cDNA) sequencing using a 3'-directed cDNA library that faithfully represents the composition of the messenger RNA (mRNA). Through a systematic search of active genes in adipose tissue, we found adiponectin, encoded by the most abundantly expressed gene in adipose tissue, termed apM1 (adipose most abundant gene transcript-1). Fat specific gene library generated in this Japanese Human Genome Project identified many other key molecules of this tissue such as leptin, PPARgamma and aP2 (adipocyte fatty acid binding protein, FABP4), in addition to apM1. Following 10 years, hundreds of clinical studies implicated the critical role of adiponectin in the metabolic syndrome. Also organized establishment of aP2 related mice model revealed the impact of this cytoplasmic fatty acid binding protein in the development of metabolic syndrome. In summary, investigating fat specific genes was amazingly powerful for analyses of the physiology of this tissue, as well as the etiology and complications of obesity.
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PMID:Role of adiponectin and adipocyte fatty acid binding protein in the metabolic syndrome. 1748 68

Adiponectin is an adipocyte-specific secretory protein that circulates in serum as three oligomeric complexes known as the high, medium and low molecular weight form (HMW, MMW and LMW). HMW adiponectin has been suggested to be a better predictor of metabolic variables, and it was recently reported that the ratio of HMW to total adiponectin or to LMW, not the absolute amount of plasma adiponectin, might be crucial in determining insulin sensitivity. Insulin resistance (IR) is considered to be a primary component of vascular risk factors. Although the association of depression with atherosclerotic vascular diseases has been well documented, the contribution of IR to the evolution and progression of depression-associated vascular morbidity and mortality remains unknown. The current preliminary study showed that the ratio of HMW to total adiponectin or to LMW, not the absolute amount of plasma adiponectin, was negatively associated with depression severity in healthy elderly subjects without metabolic syndrome. This pilot study supports a promising role of adiponectin multimer distribution for clarifying the pathophysiological mechanism by which depression is associated with increased risk for IR, leading to cardiovascular disease, metabolic syndrome or type 2 diabetes.
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PMID:Adiponectin multimer distribution, not absolute amount of plasma, correlates with depression severity in healthy elderly subjects. 1776 80

Adiponectin is an adipocyte-specific secretory protein that possesses antidiabetic and antiatherosclerotic properties. Recent studies have demonstrated that the high molecular weight (HMW) multimer form is the active form of this protein. In patients with type 2 diabetes mellitus, HMW-total adiponectin ratio was reported to be a more useful marker than total adiponectin in the prediction of insulin resistance and metabolic syndrome. In the present study of healthy Japanese male subjects without any medication, we investigated the hypothesis that measuring only HMW adiponectin may be as effective as HMW-total ratio to predict insulin resistance and/or metabolic syndrome. This was a working community-based cross-sectional study of 637 male subjects aged 30 to 65 years. Total and HMW adiponectin concentrations in serum were measured by enzyme-linked immunosorbent assay using commercially available kits. Serum HMW adiponectin level was inversely correlated with homeostasis model assessment of insulin resistance (HOMA-IR) (r = -0.375, P < .0001) even after adjustment for age and body mass index (r' = -0.245, P < .0001). When we divided the study subjects into quartile groups with equal numbers of subjects, HOMA-IR in the 4 groups based on serum HMW adiponectin level was significantly different (P < .01). Metabolic syndrome score in the 4 groups based on serum HMW adiponectin level was also significantly different (P < .01). Area under the curve of receiver operator characteristic curves of HMW adiponectin (0.73) to evaluate the presence of insulin resistance (HOMA-IR >2.5) was larger than that of total adiponectin (0.68) or HMW-total ratio (0.70). Area under the curve of receiver operator characteristic curves of HMW adiponectin (0.70) to evaluate the presence of metabolic syndrome (body mass index-based modified criteria) was also larger than that of total adiponectin (0.65), but equal to that of HMW-total ratio (0.70). These results suggest that simply measuring HMW adiponectin may be as effective as HMW-total ratio to evaluate the presence of insulin resistance and metabolic syndrome, at least in nondiabetic subjects who are not receiving any medication.
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PMID:High molecular weight multimer form of adiponectin as a useful marker to evaluate insulin resistance and metabolic syndrome in Japanese men. 1795 99


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