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 is an adipocyte-derived hormone. Recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where the gene encoding adiponectin is located. Here we show that decreased expression of adiponectin correlates with insulin resistance in mouse models of altered insulin sensitivity. Adiponectin decreases insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. This effect results from increased expression of molecules involved in both fatty-acid combustion and energy dissipation in muscle. Moreover, insulin resistance in lipoatrophic mice was completely reversed by the combination of physiological doses of adiponectin and leptin, but only partially by either adiponectin or leptin alone. We conclude that decreased adiponectin is implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy. These data also indicate that the replenishment of adiponectin might provide a novel treatment modality for insulin resistance and type 2 diabetes.
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PMID:The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. 1147 13

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

A lipodystrophic syndrome and metabolic abnormalities have been observed in HIV-infected patients treated with highly active antiretroviral therapy (HAART). A murine model of lipodystrophy is associated with decreased levels of adiponectin, an adipocyte-secreted protein, the administration of which improves the metabolic syndrome in these mice. To investigate the association of adiponectin with metabolic changes in human lipodystrophy, we conducted a cross-sectional study of 112 HIV-infected patients treated with HAART. Mean adiponectin levels were higher in patients with no fat redistribution (FR) vs. FR (4.8 +/- 5.0 vs. 2.2 +/- 2.7 microg/ml, P < 0.01), but no significant differences in adiponectin levels were observed between FR subgroups. The difference in adiponectin levels between subjects with and without FR remained significant after adjusting for age, gender, leptin, HIV medication use, and CD4 count using logistic regression (odds ratio, 0.54, P = 0.008). Adiponectin was significantly correlated with triglycerides (r = -0.40), abdominal visceral fat (r = -0.35), extremity fat (r = 0.37), insulin resistance (HOMA-IR) (r = -0.28), nucleoside reverse transcriptase inhibitor (NRTI) use (r = -0.32), and high-density lipoprotein (HDL) (r = 0.41) using bivariate analysis (all P < 0.01). The association with HDL weakened but remained significant on multivariate analysis (standard beta = 0.29, P = 0.01). However, the association of adiponectin with HOMA-IR became nonsignificant after adjusting for NRTI use (standard beta = -0.15, P = 0.12), suggesting that changes in adiponectin levels may underlie the effect of NRTI use on insulin resistance. The associations of adiponectin with triglycerides and HOMA-IR were also slightly weakened after adjusting for visceral and extremity fat, indicating that adiponectin may, in part, mediate the effect of FR on triglycerides and insulin resistance. This study indicates that adiponectin is inversely correlated with abdominal visceral fat mass, serum triglycerides, and insulin resistance and is directly correlated with HDL and extremity fat in a sample of HIV-infected patients treated with HAART. The results also indicate that NRTI use may worsen insulin resistance by decreasing adiponectin levels. Thus, adiponectin replacement may be a potential treatment option to ameliorate the metabolic changes observed in this patient population.
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PMID:Hypoadiponectinemia is associated with insulin resistance, hypertriglyceridemia, and fat redistribution in human immunodeficiency virus-infected patients treated with highly active antiretroviral therapy. 1257 92

Insulin resistance and hyperinsulinemia are known atherosclerosis risk factors. The association between adiponectin plasma levels and obesity, insulinemia, and atherosclerosis has been shown. Thus, adiponectin may be a link between hyperinsulinemia and vascular disease. In vitro data demonstrated a reduction of adiponectin expression by insulin. However, it is still unclear whether insulin regulates adiponectinemia in vivo in humans. Five healthy male volunteers were studied. Circulating adiponectin levels were determined before and during hyperinsulinemic euglycemic clamp. Adiponectin was measured by radioimmunoassay. Hyperinsulinemia (85.0 +/- 33.2 at baseline vs. 482.8 +/- 64.4 pmol/l during steady state; p < 0.01) was achieved using a euglycemic hyperinsulinemic clamp, keeping blood glucose levels basically unchanged during the intervention (4.6 +/- 0.14 vs. 4.37 +/- 0.15 mmol/l, respectively; ns). We found a significant decrease of adiponectin plasma levels during the steady state of hyperinsulinemic euglycemic clamp (26.7 +/- 3.5 micro g/ml) compared to baseline levels (30.4 +/- 5 micro g/ml; p < 0.05). Hyperinsulinemia caused a significant decrease of adiponectin plasma levels under euglycemic conditions. Considering existing data about adiponectin dependent effects, hypoadiponectinemia might at least partly be a link between hyperinsulinemia and vascular disease in metabolic syndrome.
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PMID:Insulin decreases human adiponectin plasma levels. 1266 Aug 77

Adiponectin is an insulin-sensitizing hormone whose blood concentration is reduced in obesity and type 2 diabetes. Administration of recombinant adiponectin in rodents increases glucose uptake and increases fat oxidation in muscle, reduces fatty acid uptake and hepatic glucose production in liver, and improves whole body insulin resistance. The exact receptor and signaling systems are unknown, however, recent studies suggest adiponectin activates AMPK, a putative master metabolic regulator. Thus, excitement surrounds the potential for adiponectin, or a homologue of adiponectin, as pharamacotherapy agents for patients suffering from the metabolic syndrome and more particularly for individuals with insulin resistance and type 2 diabetes.
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PMID:The insulin-sensitizing role of the fat derived hormone adiponectin. 1276 32

Adiponectin, an adipocyte-derived protein, consists of collagen-like fibrous and complement C1q-like globular domains, and circulates in human plasma in a multimeric form. The protein exhibits anti-diabetic and anti-atherogenic activities. However, adiponectin plasma concentrations are low in obese subjects, and hypoadiponectinemia is associated with the metabolic syndrome, which is a cluster of insulin resistance, type 2 diabetes mellitus, hypertension, and dyslipidemia. We have recently reported a missense mutation in the adiponectin gene, in which isoleucine at position 164 in the globular domain is substituted with threonine (I164T). Subjects with this mutation showed markedly low level of plasma adiponectin and clinical features of the metabolic syndrome. Here, we examined the molecular characteristics of the mutant protein associated with a genetic cause of hypoadiponectinemia. The current study revealed (1) the mutant protein showed an oligomerization state similar to the wild-type as determined by gel filtration chromatography and, (2) the mutant protein exhibited normal insulin-sensitizing activity, but (3) pulse-chase study showed abnormal secretion of the mutant protein from adipose tissues. Our results suggest that I164T mutation is associated with hypoadiponectinemia through disturbed secretion into plasma, which may contribute to the development of the metabolic syndrome.
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PMID:Disturbed secretion of mutant adiponectin associated with the metabolic syndrome. 1278 2

Adiponectin is an adipose-derived plasma protein. Recently the plasma adiponectin levels have been linked to most variables of metabolic syndrome (MS) and risk factors of coronary artery disease (CAD). However, its relation with blood pressure is yet unclear. Here we report the relationship between the plasma adiponectin levels and blood pressures in 68 female adolescents (age 16.1 +/- 1.8 yr). We found that the plasma adiponectin levels correlated significantly with both the systolic blood pressure (SBP) (gamma = -0.47, P = 0.000) and diastolic blood pressure (gamma = -0.30, P = 0.014). In linear regression models with adjustment for age and the other anthropometric or metabolic factors, only the SBP, but not the diastolic blood pressure, was independently related to the plasma adiponectin levels. The mean plasma adiponectin levels between the subjects in the lowest quartile of SBP (SBP < or = 100 mm Hg) and those in the highest quartile (SBP > or = 118 mm Hg) were significantly different (P = 0.035). In conclusion, the SBP is inversely related to the plasma adiponectin independent of the other variables of the MS and other risk factors of CAD in healthy adolescent females. This further strengthens the potential roles of adiponectin in the pathophysiology of MS and CAD.
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PMID:Plasma adiponectin levels and blood pressures in nondiabetic adolescent females. 1297 Feb 75

In this review article, the crucial roles of adipocytes in the development of so-called metabolic syndrome and vascular disease are reviewed, focusing on adipocyte-derived bioactive substances, adipocytokines. Recent progress in adipocyte biology shows that adipocytes are not merely energy-storing cells but that they secrete a variety of hormones cytokines, growth factors, and other bioactive substances. To search for novel adipocytokines by the large-scale random sequence analysis of expressed genes in adipocytes, we identified an adipose-specific collagen-like molecule, adiponectin. This novel adipocytokine has plural biofunctions, such as antidiabetic, antiatherosclerotic, and antiinflammatory functions. Adiponectin plasma levels decrease with the accumulation of visceral adipose tissue. In this review, we discuss the link of adiponectin to visceral adiposity, insulin resistance, and vascular diseases.
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PMID:Adiponectin and metabolic syndrome. 1455 Nov 51

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


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