Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HIV-related lipodystrophy is characterized by adipose redistribution, dyslipidemia, and insulin resistance. Adiponectin is an adipose-derived peptide thought to act as a systemic regulator of glucose and lipid metabolism. We investigated adiponectin concentrations in 10 HIV-infected patients during acute HIV infection (viral load, 2.0 x 10(6) +/- 1.0 x 10(6) copies/ml) and then 6-8 months later, as well as cross-sectionally in 41 HIV-infected patients (21 with evidence of fat redistribution and 20 without evidence of fat redistribution) in comparison with 20 age- and body mass index-matched healthy control subjects. Circulating adiponectin concentrations did not change with treatment of acute HIV infection (5.8 +/- 0.4 vs. 5.9 +/- 0.7 micro g/ml, P = 0.96) but were reduced in patients with chronic HIV infection and fat redistribution (7.8 +/- 0.9 micro g/ml), compared with age- and body mass index-matched HIV-infected patients without fat redistribution (12.7 +/- 1.7 micro g/ml) and healthy control subjects (11.9 +/- 1.7 micro g/ml, P < 0.05 vs. HIV-infected patients without fat redistribution and vs. control subjects). Adiponectin concentrations correlated with body composition [correlation coefficient (r) = -0.47, P = 0.002 vs. trunk fat:total fat; r = 0.51, P < 0.001 vs. extremity fat:total fat], insulin response to glucose challenge (r = -0.36, P = 0.03), triglyceride (r = -0.39, P = 0.01), and high-density lipoprotein (r = 0.37, P = 0.02) among the HIV-infected patients. Adiponectin remained a significant correlate of insulin response to GTT, controlling for medication use and body composition changes in HIV-infected patients. These data suggest a strong relationship between adiponectin and body composition in HIV-infected patients. Changes in adiponectin may contribute to the metabolic dysregulation in this group of patients.
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PMID:Regulation of adiponectin in human immunodeficiency virus-infected patients: relationship to body composition and metabolic indices. 1267 39

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

Cardiovascular disease accounts for an overwhelming proportion of the morbidity and mortality suffered by patients with obesity and type 2 diabetes mellitus, and recent work has elucidated several potential mechanisms by which increased adiposity enhances cardiovascular risk. Excess adipose tissue, especially in certain compartments, leads to reduced insulin sensitivity in metabolically responsive tissues, which is frequently associated with a set of cardiovascular risk factors, including hyperinsulinemia, hypertension, dyslipidemia, and glucose intolerance. Increasing attention has also been paid to the direct vascular effects of plasma proteins that originate from adipose tissue, especially adiponectin, which exhibits potent antiinflammatory and antiatherosclerotic effects. This brief review will summarize recent work on the vascular actions of adiponectin, which complements the growing body of information on its insulin-sensitizing effects in glucose and lipid metabolism. Adiponectin is now a recognized component of a novel signaling network among adipocytes, insulin-sensitive tissues, and vascular function that has important consequences for cardiovascular risk.
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PMID:Adiponectin: A novel adipokine linking adipocytes and vascular function. 1518 Oct 24

Adiponectin is a plasma protein exclusively secreted from fat tissue. Many recent pharmacological studies suggest that recombinant adiponectin has multiple therapeutic potentials for obesity-related metabolic disorders, including type 2 diabetes, dyslipidemia, insulin resistance and atherosclerosis. However, the physiological relevance of these findings remains to be further established. In the present study, we have purified endogenous adiponectin from fetal bovine serum and characterized its post-translational modifications and physiological functions in animal models. Endogenous bovine serum adiponectin consists predominantly of full-length proteins that form multiple oligomeric complexes, including trimers, hexamers and higher molecular species. Two-dimensional gel electrophoresis revealed that bovine serum adiponectin exists as multiple post-translationally modified isoforms with distinct molecular weight and isoelectric point. Further analysis using mass spectrometry and Edman degradation sequencing demonstrated that five conserved lysine residues (Lys 28, 60, 63, 72 and 96) within the collagenous domain of bovine adiponectin are hydroxylated and glycosylated by a glucosyl alpha(1-2)galactosyl group. Injection of endogenous bovine adiponectin into C57 mice potently decreased circulating glucose levels and enhanced lipid clearance after a high fat meal. Chronic administration of this protein for a period of two weeks significantly increased insulin sensitivity and glucose tolerance, and depleted hepatic lipid accumulation in high-fat fed mice. These results provide direct evidence that endogenous bovine adiponectin is a physiological hormone that can regulate lipid and glucose metabolism.
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PMID:Proteomic and functional characterization of endogenous adiponectin purified from fetal bovine serum. 1537 92

Adiponectin, predominantly synthesized in the adipose tissue, seems to have substantial anti-inflammatory properties and to be a major modulator of insulin resistance and dyslipidemia, mechanisms that are associated with an increased atherosclerotic risk in diabetic patients. However, it is unknown whether higher levels of adiponectin are associated with a reduced risk for coronary heart disease (CHD) among diabetic individuals. We investigated the association between plasma adiponectin levels and incidence of CHD among 745 men with confirmed type 2 diabetes in the Health Professionals Follow-up Study. Participants were aged 46-81 years and were free of diagnosed cardiovascular disease at the time of blood draw in 1993/1994. During an average of 5 years of follow-up (3,980 person-years), we identified 89 incident cases of CHD (19 myocardial infarction and 70 coronary artery bypass surgery), confirmed by medical records. Levels of adiponectin were inversely associated with BMI and directly associated with age, alcohol intake, and duration of diabetes (P < 0.05). After adjustment for age, BMI, smoking, alcohol consumption, duration of diabetes, and other lifestyle factors, adiponectin was associated with a decreased risk for CHD events. The multivariate relative risk for CHD for a doubling of adiponectin was 0.71 (95% CI 0.53-0.95). Further adjustment for HDL cholesterol attenuated this association (0.78 [0.57-1.06]). The inverse association between adiponectin and CHD was consistent across strata of aspirin use, family history of myocardial infarction, alcohol consumption, insulin use, duration of diabetes, and levels of HbA(1c), triglycerides, C-reactive protein, and HDL cholesterol. Our study suggests that increased adiponectin levels are associated with a moderately decreased CHD risk in diabetic men. This association seems to be mediated in part by effects of adiponectin on HDL cholesterol levels.
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PMID:Adiponectin and future coronary heart disease events among men with type 2 diabetes. 1567 12

The aim of the study was to assess the relation of adiponectin levels with the metabolic syndrome in Asian Indians, a high-risk group for diabetes and premature coronary artery disease. The study was conducted on 100 (50 men and 50 women) type 2 diabetic subjects and 100 age and sex matched subjects with normal glucose tolerance selected from the Chennai Urban Rural Epidemiology Study, an ongoing population study in Chennai in southern India. Metabolic syndrome was defined using modified Adult Treatment Panel III (ATPIII) guidelines. Adiponectin values were significantly lower in diabetic subjects (men: 5.2 vs 8.3 microg/mL, P=.00l; women: 7.6 vs 11.1 microg/mL, P<.00l) and those with the metabolic syndrome (men: 5.0 vs 6.8 microg/mL, P=.01; women: 6.5 vs 9.9 microg/mL, P=.001) compared with those without. Linear regression analysis revealed adiponectin to be associated with body mass index (P<.05), waist circumference (P<.01), fasting plasma glucose (P=.001), glycated hemoglobin (P<.001), triglycerides (P<.00l), high-density lipoprotein (HDL) cholesterol (P<.001), cholesterol/HDL ratio (P<.00l), and insulin resistance measured by homeostasis assessment model (P<.00l). Factor analysis identified 2 factors: factor 1, negatively loaded with adiponectin and HDL cholesterol and positively loaded with triglycerides, waist circumference, and insulin resistance measured by homeostasis assessment model; and factor 2, with a positive loading of waist circumference and systolic and diastolic blood pressure. Logistic regression analysis revealed adiponectin to be negatively associated with metabolic syndrome (odds ratio [OR], 0.365; P<.001) even after adjusting for age (OR, 0.344; P<.00l), sex (OR, 0.293; P<.001), and body mass index (OR, 0.292; P<.00l). Lower adiponectin levels are associated with the metabolic syndrome per se and several of its components, particularly, diabetes, insulin resistance, and dyslipidemia in this urban south Indian population.
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PMID:Association of low adiponectin levels with the metabolic syndrome--the Chennai Urban Rural Epidemiology Study (CURES-4). 1579 54

Adiponectin is a plasma protein produced by the adipose tissue. Hypoadiponectinemia has been associated with insulin resistance and several components of the metabolic syndrome (MS): type 2 diabetes, obesity, and dyslipidemia. We investigated whether single nucleotide polymorphisms (SNPs) at positions 45 and 276 in the adiponectin gene were associated with features of the MS in 747 unrelated Spanish subjects. The G allele of SNP45 and the G/G genotype of SNP276 were associated with impaired glucose tolerance (p = 0.020 and 0.042, respectively). The G/G genotype for SNP276 was associated with lower serum adiponectin levels as compared with the G/T and T/T genotypes (G/G, 10.10 +/- 0.24 microg/mL; G/T, 10.98 +/- 0.32 microg/mL; T/T, 12.00 +/- 0.92 microg/mL; p = 0.015) even after adjustment for sex, age, BMI, waist-to-hip ratio, homeostasis model assessment index, and the degree of glucose tolerance (p = 0.040). We found a significant negative association of circulating adiponectin levels with waist-to-hip ratio (r = -0.42, p < 0.001), sagittal abdominal diameter (r = -0.24, p < 0.001), triglycerides (r = -0.32, p < 0.001), homeostasis model assessment index (r = -0.14, p = 0.001), and uric acid (r = -0.36, p < 0.001) and positive association with high-density lipoprotein-cholesterol (r = 0.41, p < 0.001). Our findings indicate that serum adiponectin levels are associated with several components of the MS. The SNP276 of the adiponectin gene may affect impaired glucose tolerance and hypoadiponectinemia.
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PMID:An SNP in the adiponectin gene is associated with decreased serum adiponectin levels and risk for impaired glucose tolerance. 1591 31

Adiponectin is a serum protein secreted by adipocytes and accounts for approximately 0.01% of total plasma protein. In healthy patient populations adiponectin can be found in concentrations of 7-12 mg/l. Unlike other adipocyte products, adiponectin correlates with decreased free fatty acid blood concentrations and reduced body mass index or body weight. Adiponectin protects from vascular diseases by inhibiting local proinflammatory signals, preventing preatherogenic plaque formation, and by impeding arterial wall thickening. Proinflammatory state and endothelial dysfunction are nominators of the metabolic syndrome, a complex set of risk factors including vascular and metabolic insulin resistance with hyperglycemia, hypertension, and dyslipidemia. Over the past years, thiazolidinediones, like rosiglitazone or pioglitazone, became known as a therapeutic option for patients suffering from the metabolic syndrome. It is considered that insulin sensitizers exert their benefit through indirect induction of adiponectin expression. Clinical studies have confirmed that treatment with thiazolidinediones may increase adiponectin concentrations in patients with type 2 diabetes independent from improvements in blood glucose control or parallel treatment with insulinotropic drugs. These findings suggest that adiponectin may have a diagnostic value and can be used especially for monitoring treatment success. This review summarizes recent biological and clinical data indicating that adiponectin may be the molecular link between obesity and insulin resistance and may serve as a biomarker for the metabolic syndrome.
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PMID:Biological background and role of adiponectin as marker for insulin resistance and cardiovascular risk. 1628 70

Adiponectin, an adipose-derived plasma protein, has been well established to be an important biomarker for metabolic syndrome and its complications after exhausted studies in humans. Animal and cell culture experiments also support most claims from human observations of its roles in the metabolic syndrome. Reproducible results of human genetic studies of diverse ethnic origin and by different investigators may provide the evidence for its causative roles in the pathogenesis of the metabolic syndrome and further insight into the genetic constitutions of the metabolic syndrome. Some of the common polymorphisms in the promoter region, exon and intron 2, and the rare nonsynonymous mutations in exon 3 of the human adiponectin gene were repeatedly shown in many studies from many different ethnic populations to associate with the phenotypes related to body weight, glucose metabolism, insulin sensitivity, and risk of type 2 diabetes mellitus and coronary artery disease. The association of adiponectin genetic variations with dyslipidemia and blood pressure was less explored. The common polymorphisms and rare mutations of the human adiponectin gene itself were demonstrated to associate with differential expression of adiponectin at the plasma protein level and mRNA level in adipose tissue. The PPARgamma2 Pro12Ala variants were also shown to influence insulin sensitivity in interaction with adiponectin genotype or to influence plasma adiponectin levels. However, the results were not consistent. Three genome-wide scans for the loci that regulate plasma adiponectin concentration suggest further exploration on chromosomes 5, 9, 14, 15, and 18 is required. These human genetic studies on adiponectin and the metabolic syndrome strongly suggest that adiponectin is one of the causative factors in its pathogenesis and provide significant insights into the genetic makeup of the metabolic syndrome. Extension from these studies may accelerate the discovery of new molecular targets for future therapeutic interventions.
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PMID:Human genetics of adiponectin in the metabolic syndrome. 1638 53

The obesity epidemic has focused attention on the endocrine function of adipose tissue. Adipose tissue secretes leptin, cytokines, complement factors, and components of the coagulation cascade, most of which are increased in obesity. In contrast, a strong negative correlation exists between adiponectin and adiposity, insulin sensitivity, diabetes, vascular inflammation, and atherosclerosis. Adiponectin treatment in rodents increases insulin sensitivity and reduces lipids and atherogenesis. Chronic and central adiponectin treatment reduces weight, glucose, and lipids. The insulin-sensitizing action of thiazolidinediones is mediated, in part, through adiponectin. A causal role of adiponectin in diabetes, dyslipidemia, and atherosclerosis has been established in knockout mice. Therefore, adiponectin seems to be a marker of obesity-related diseases and a potential therapeutic target.
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PMID:Metabolic actions of adipocyte hormones: focus on adiponectin. 1664 57


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