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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Visceral fat accumulation often accompanies various complications, such as insulin resistance, hypertension, dyslipidemia and atherosclerosis. Adipose tissue has been found to secrete various biologically active adipocytokines including free fatty acids. Accumulation of visceral fat increases the portal free fatty acids concentration to cause insulin resistance and dyslipidemia. Tumor necrosis alpha (TNF alpha) deteriorates insulin resistance in obesity. The levels of plasminogen activator inhibitor(PAI)-1 increase and plasma adiponectin concentration decreases in obesity leading to the development of vascular disease. The finding of genes specifically expressed in visceral fat and new adipocytokines should facilitate clarification of the mechanism for the development and complications of visceral fat accumulation.
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PMID:[Molecular mechanism in the development of the complications associated with obesity--the physiological and pathological role of adipocytokines]. 1126 96

Insulin resistance is a major contributor to the pathogenesis of type 2 diabetes and plays a key role in associated metabolic abnormalities, such as dyslipidemia and hypertension. Obesity, especially visceral adiposity, is negatively correlated with insulin sensitivity. The release of free fatty acids from adipocytes can block insulin-signaling pathways and lead to insulin resistance. In addition, recently identified adipocyte-specific chemical messengers, the adipocytokines, such as tumor necrosis factor-alpha, adiponectin, and resistin, appear to modulate the underlying insulin resistance. When insulin resistance is combined with beta-cell defects in glucose-stimulated insulin secretion, impaired glucose tolerance, hyperglycemia, or type 2 diabetes can result. The thiazolidinediones are potent peroxisome proliferator-activated receptor-gamma agonists and directly improve insulin resistance and glycemic control in patients with type 2 diabetes. Increasing evidence supports the early use of thiazolidinediones for preventing, delaying, or treating diabetes by improving insulin sensitivity and beta-cell insulin secretion.
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PMID:Insulin resistance as the core defect in type 2 diabetes mellitus. 1223 Oct 73

Adipocytes have traditionally been considered to be the primary site for whole body energy storage mainly in the form of triglycerides and fatty acids. This occurs through the ability of insulin to markedly stimulate both glucose uptake and lipogenesis. Conventional wisdom held that defects in fuel partitioning into adipocytes either because of increased adipose tissue mass and/or increased lipolysis and circulating free fatty acids resulted in dyslipidemia, obesity, insulin resistance and perhaps diabetes. However, it has become increasingly apparent that loss of adipose tissue (lipodystrophies) in both animal models and humans also leads to metabolic disorders that result in severe states of insulin resistance and potential diabetes. These apparently opposite functions can be resolved by the establishment of adipocytes not only as a fuel storage depot but also as a critical endocrine organ that secretes a variety of signaling molecules into the circulation. Although the molecular function of these adipocyte-derived signals are poorly understood, they play a central role in the maintenance of energy homeostasis by regulating insulin secretion, insulin action, glucose and lipid metabolism, energy balance, host defense and reproduction. The diversity of these secretory factors include enzymes (lipoprotein lipase (LPL) and adipsin), growth factors [vascular endothelial growth factor (VEGF)], cytokines (tumor necrosis factor-alpha, interleukin 6) and several other hormones involved in fatty acid and glucose metabolism (leptin, Acrp30, resistin and acylation stimulation protein). Despite the large number of molecules secreted by adipocytes, our understanding of the pathways and mechanisms controlling intracellular trafficking and exocytosis in adipocytes is poorly understood. In this article, we will review the current knowledge of the trafficking and secretion processes that take place in adipocytes, focusing our attention on two of the best characterized adipokine molecules (leptin and adiponectin) and on one of the most intensively studied regulated membrane proteins, the GLUT4 glucose transporter.
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PMID:An adipocentric view of signaling and intracellular trafficking. 1239 77

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

Lipodystrophy (LD) is a well-recognised clinical syndrome of peripheral fat atrophy and central adiposity, often associated with laboratory abnormalities such as dyslipidemia and glucose intolerance, and probably linked to insulin resistance. The long-term consequences of LD and its potential association with cardiovascular disease remain unknown. The visceral fat accumulation is characterised by the increased, abundant secretion of a number of peptides such as leptin, insulin-like growth factor (IGF), adiponectin and the recently reported resistin and visfatin hormones. Elevated resistin and tumour necrosis factor (TNF-alpha) levels and low levels of adiponectin secretion may have implications for the risk of development of type 2 diabetes and cardiovascular disease. LD is observed not only in rare autosomal syndromes, but also in patients positive for the human immunodeficiency virus (HIV) who have been treated with protease inhibitors. Both the origin of LD and its treatment deserve more attention and further research in clinical settings.
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PMID:Health risks of lipodystrophy and abdominal fat accumulation: therapeutic possibilities with leptin and human growth hormone. 1291 18

Normal metabolic balance is maintained by a complex homeostatic system involving multiple tissues and organs. Acquired or inherited defects associated to environmental factors in any part of this system can lead to metabolic disorders such as the syndrome X which is presently a frequent syndrome in industrialized countries. It is characterized by a cluster of risk factors of atherosclerosis including insulin resistance, hyperinsulinemia, impaired glucose tolerance or type 2 diabetes, hypertension, dyslipidemia, and coagulation abnormalities. Its pathophysiology is likely to involve insulin resistance at the level of both skeletal muscle and visceral adipose tissue and altered fluxes of metabolic substrates between these tissues that in turn impair liver metabolism. Therapeutic intervention favours at present diet and exercise prescriptions. In addition, if necessary, specific treatment of the metabolic disorders is required. In the treatment of insulin resistance, new promising drugs are likely to be used in the next future. In this regard, adipose tissue, once thought to function primarily as a passive depot for the storage of excess lipid, is now understood to play a much more active role in metabolic regulation, secreting a variety of metabolic hormones and actively functioning to prevent deleterious lipid accumulation in other tissues and to modulate the insulin resistance. Here, we review new advances in our understanding of mechanisms leading to insulin resistance and type 2 diabetes from the perspective of the role and interactions of recently identified adipocyte-specific chemical messengers, the adipocytokines, such as adiponectin, tumor necrosis factor-alpha, interleukin 6, and resistin.
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PMID:[Adipocytokins, obesity and development of type 2 diabetes]. 1459 11

Syndrome X, typified by obesity, insulin resistance (IR), dyslipidemia, and other metabolic abnormalities, is responsive to antidiabetic thiazolidinediones (TZDs). Peroxisome proliferator-activated receptor (PPAR) gamma, a target of TZDs, is expressed abundantly in adipocytes, suggesting an important role for this tissue in the etiology and treatment of IR. Targeted deletion of PPARgamma in adipose tissue resulted in marked adipocyte hypocellularity and hypertrophy, elevated levels of plasma free fatty acids and triglyceride, and decreased levels of plasma leptin and ACRP30. In addition, increased hepatic glucogenesis and IR were observed. Despite these defects, blood glucose, glucose and insulin tolerance, and insulin-stimulated muscle glucose uptake were all comparable to those of control mice. However, targeted mice were significantly more susceptible to high-fat diet-induced steatosis, hyperinsulinemia, and IR. Surprisingly, TZD treatment effectively reversed liver IR, whereas it failed to lower plasma free fatty acids. These results suggest that syndrome X may be comprised of separable PPARgamma-dependent components whose origins and therapeutic sites may reside in distinct tissues.
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PMID:Adipose-specific peroxisome proliferator-activated receptor gamma knockout causes insulin resistance in fat and liver but not in muscle. 1466 Jul 88

The prevalence of overweight and obesity continues to increase rapidly in the United States, with more than half of all adults currently overweight or obese. In general, people become obese because of a combination of inherited genes and a lifestyle consisting of low levels of physical activity and consumption of excess calories. Obesity, especially the central or visceral type, is a predisposing factor for the development of type 2 diabetes mellitus, hypertension, and cardiovascular disease (CVD). Obesity and type 2 diabetes are associated with insulin resistance. The relation among obesity, insulin resistance, and CVD appears to develop at a relatively young age. Central obesity is linked with hyperinsulinemia, insulin resistance, dyslipidemia, and proinflammatory and prothrombotic clinical states. Adipose tissue synthesizes and secretes biologically active molecules that may affect CVD risk factors. These chemical messengers include adiponectin, resistin, leptin, plasminogen activator inhibitor-1, tumor necrosis factor-alpha, and interleukin-6. In overweight and obese individuals, weight loss may improve insulin sensitivity, leading to reduction in risk factors for CVD and, consequently, the potential for cardiovascular events. Agents that improve insulin sensitivity, such as the thiazolidinediones, have been shown to reduce visceral obesity. Decreases in visceral adipose tissue contribute to improvements in insulin sensitivity and blood pressure, and weight loss reduces serum levels of triglycerides and low-density lipoprotein cholesterol while increasing serum levels of high-density lipoprotein cholesterol. Reduction of risk factors suggests that the development of cardiovascular disease will be reduced by the improvement of insulin sensitivity and weight loss.
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PMID:Obesity as a cardiovascular risk factor. 1467 64

White adipose tissue (WAT) plays a critical role in the development of insulin resistance via secretion of free fatty acids (FFA) and adipocytokines. Muscle-specific insulin receptor knockout (MIRKO) mice do not develop insulin resistance or diabetes under physiological conditions despite a marked increase in adiposity and plasma FFA. On the contrary, WAT of MIRKO is sensitized to insulin action during a euglycemic clamp, and WAT glucose utilization is dramatically increased. To get insight into the potential antidiabetic role of MIRKO adiposity, we have studied insulin action in WAT during a euglycemic, hyperinsulinemic clamp, and we have characterized the morphology and biology of WAT. During the clamp, there is no alteration in the expression or activation in the insulin signaling molecules involved in glucose transport through the phosphoinositide 3-kinase/Akt and CAP/Cbl pathways in WAT from MIRKO. The 53% increase in WAT mass results from a 48% increase in adipocyte number (P < 0.05) without alteration in cell size and contemporary to a 300% increase in mRNA levels of the adipogenic transcription factor CCAAT enhancer binding protein-alpha (C/EBP-alpha) (P < 0.05). There is a 39.5% increase in serum adiponectin (P < 0.01) without modification in serum leptin, resistin, and TNF-alpha. In conclusion, the MIRKO mouse displays muscle insulin resistance, visceral obesity, and dyslipidemia but does not develop hyperinsulinemia or diabetes. There is an accelerated differentiation of small insulin sensitive adipocytes, an increased secretion of the insulin sensitizer adiponectin, and maintenance of leptin sensitivity. The MIRKO mouse confirms the importance of WAT plasticity in the maintenance of whole body insulin sensitivity and represents an interesting model to search for new secreted molecules that positively alter adipose tissue biology.
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PMID:Cellular and molecular mechanisms of adipose tissue plasticity in muscle insulin receptor knockout mice. 1468 12


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