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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For a long time it has been known that obesity (adiposity) is linked to insulin resistance. Recently, many investigators have reported that adipocytes secrete a variety of bioactive molecules, termed adipokines (adipocytokines), including TNFalpha, IL-6, leptin, adiponectin, resistin and so on. These adipokines play pivotal roles in energy homeostasis by affecting insulin sensitivity, glucose and lipid metabolisms, food intake, the coagulation system and inflammation. This review provides a summary of these adipose tissue-secreting biomolecules and discusses their feasibilities as drug targets for the treatment of metabolic syndrome.
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PMID:Adipokines: therapeutic targets for metabolic syndrome. 1602 71

White adipose tissue (WAT) is now recognized as a major endocrine and secretory organ, releasing a wide range of protein factors and signals termed adipokines - in addition to fatty acids and other lipid moieties. A paradigm shift came with the discovery of leptin, a pleiotropic hormone which is a critical signal to the hypothalamus in the control of appetite and energy balance. A number of adipokines, including adiponectin, tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1, macrophage migration inhibitory factor, nerve growth factor, vascular endothelial growth factor, plasminogen activator inhibitor-1 and haptoglobin, are linked to inflammation and the inflammatory response. Obesity is characterized by a state of mild inflammation, and the expression and release of inflammation-related adipokines generally rises as adipose tissue expands; a notable exception is adiponectin, with its anti-inflammatory action, the levels of which fall. WAT may be the main site of inflammation in obesity, increased circulating levels of inflammatory markers reflecting spillover from an 'inflamed' tissue, leading to the obesity-associated pathologies of type 2 diabetes and the metabolic syndrome. From the wide range of adipokines now identified, it is evident that WAT is highly integrated into overall physiological regulation, involving extensive crosstalk with other organs and multiple metabolic systems. Whether major changes in adipokine production in obesity, particularly of those factors linked to inflammation, are unique to this condition, or are a feature of all situations in which there are substantial increases in adipose mass (such as pregnancy, and pre-hibernatory and pre-migratory fattening) requires consideration.
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PMID:Endocrine and signalling role of adipose tissue: new perspectives on fat. 1602 20

The combined effect of Peroxisome proliferator-activated receptor gamma (PPARG) Pro/Ala and interleukin-6 G174C gene variants, was evaluated in 429 Caucasian subjects in order to determine whether subjects carrying both variants were at different risk for obesity. In particular, the combined contribution of these two variants (both independent and interaction effects) to the total variation of obesity-related factors was estimated. All subjects were genotyped for codon 12 Pro/Ala locus variability and for the interleukin-6-174 C/G promoter polymorphism. Subjects with the Ala variant had significantly lower BMI, insulin resistance, triglyceride levels than those without. Furthermore, subjects with Ala variant had significantly lower IL-6 levels (0.88 +/- 0.9 vs 1.61 +/- 2.25 pg/ml; p = 0.041). In contrast, the IL6-C variant was significantly associated with lower plasma IL-6 and with lower total cholesterol levels but was not significantly associated with any other obesity risk factors. Indeed, subjects carrying both PPARG and IL-6 gene variants, had a clearly more favourable profile of obesity related risk factors than subjects with one variant, having Ala+/C+ carriers lower BMI (22.8 +/- 2.3 vs 24.14 +/- 1.9; f = 5.31; p < 0.005), insulin resistance (1.49 +/- 0.70 vs 2.13 +/- 0.92; f = 4.342; p = 0.038) and triglyceride levels (79.15 +/- 32.9 vs 98 +/- 6.73 mg/dl; f = 3.120; p < 0.005). These findings suggest that the effect of the two genetic variants on 'obesity related' factors is additive.
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PMID:Role of interaction between variants in the PPARG and interleukin-6 genes on obesity related metabolic risk factors. 1602 43

Type 2 diabetes is associated with a systemic low-grade inflammation. First data provided by cross-sectional studies from as early as the 1960s demonstrated elevated systemic levels of glycoproteins and acute-phase reactants and increased leukocyte counts in type 2 diabetes patients. Subsequently, prospective studies showed that elevated concentrations of several acute-phase proteins and cytokines are predictive of later type 2 diabetes. Immune gene variants in man and in animal models were found to affect insulin resistance and diabetes incidence. Antidiabetic treatment by medication, diet or physical activity results in a significant decrease of systemic immune mediator concentrations. Immunological analyses of the KORA Survey S4 (1999/2001) allowed us to show that levels of circulating acute-phase proteins like CRP and of IL-6 are highly correlated and associated not only with overt type 2 diabetes, but already with impaired glucose tolerance (IGT) pointing out a role of these mediators in the pathogenesis of type 2 diabetes. On the contrary, TNFalpha was neither coregulated with CRP nor associated with diabetes status. Our study therefore shows that type 2 diabetes is accompanied by a non-random and differential upregulation of components of the innate immunity and suggests that this inflammatory condition is involved in the aetiology of the disease. Future work will extend the range of analysed immune mediators to chemokines and will also investigate the association of immune markers with indices of obesity to elucidate the relevance of this traditional risk factor for low-grade inflammation.
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PMID:Inflammation and type 2 diabetes: results from KORA Augsburg. 1603 28

It has been recognized for some time that cardiovascular disease and type 2 diabetes are, to a major extent, inflammatory disorders associated with an environment characterized by a sedentary lifestyle together with abundant intakes of calories. Systemic low-level inflammation is suggested to be a cause as well as consequence of pathological processes with local tumor necrosis factor alpha production as an important biological driver. It is hypothesized that physical inactivity contributes to an enhanced proinflammatory burden independently of obesity, as regular muscle contractions mediate signals with myokines/cytokines as important messengers, which suppress proinflammatory activity at distant sites as well as within skeletal muscle. Muscle-derived interleukin (IL)-6 is considered to possess a central role in anti-inflammatory activities and health beneficial effects in relation to physical exercise. It is discussed how this fits the consistent observation that enhanced plasma levels of IL-6 represent a strong risk marker in chronic disorders associated with systemic low-level inflammation and all-cause mortality.
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PMID:Physical activity and modulation of systemic low-level inflammation. 1603 12

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

It has not yet been shown in prepubertal children how cytokines, leptin, and body mass, as well as parameters of obesity are interrelated. The aim of this study was to explore the relation between circulating levels of some cytokines with leptin and body mass index. A case control study was carried out in obese children of both sexes. An obese group was carried out with 63 school prepubertal children and a control group comprised the same number of nonobese children paired by age and by sex. Mean serum leptin concentration was significantly higher in the obese children at 19.9 +/- 7.4 ng/mL, than the control group (7.9 +/- 5.1 ng/mL). Serum IL-1beta, IL-6, and TNF-alpha levels were also significantly higher in the obese group than controls (33.0 +/- 8.9, 45.2 +/- 11.8, and 9.2 +/- 2.3 pg/mL, versus 3.6 +/- 1.0, 13.1 +/- 3.9, and 3.9 +/- 1.0 pg/mL, resp). In controversy, serum IL-2 level was diminished in the obese group as 0.4 +/- 0.1 versus 0.9 +/- 0.1 U/L. Obesity may be a low-grade systemic inflammatory disease. Obese prepubertal children have elevated serum levels of IL-1beta , IL-6, and TNF-alpha which are known as markers of inflammation.
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PMID:Proinflammatory cytokines and leptin are increased in serum of prepubertal obese children. 1610 6

Elevated plasma IL-18 is present in several conditions sharing insulin-resistance as common trait, but the association with insulin-resistance per se is not established. Plasma/serum IL-6, IL-18, TNF-alpha, soluble TNF receptor II (sTNFR2), and C-reactive protein (CRP) were measured in 97 patients with type 2 diabetes (DM) and 84 non-diabetic controls (CON). The association with insulin-resistance-estimated using the homeostasis model assessment (HOMA-IR)-was analyzed using multivariate linear and logistic regression. Compared to CON, DM demonstrated higher plasma levels of IL-18 (P = 0.001), IL-6 (P < 0.001), sTNFR2 (P = 0.005), and CRP (P < 0.001), while TNF-alpha was lower (P = 0.017). Plasma IL-18 increased across HOMA-IR quartiles in both DM and CON, both with and without adjustment for confounders (all P < 0.05). In contrast, neither IL-6, TNF-alpha, sTNFR2, nor CRP was associated with HOMA-IR in CON when adjusting for confounders. Accordingly, 50% increase of IL-18 corresponded to a marked increase of HOMA-IR in both DM and CON (DM: 26%, P = 0.014; CON: 25%, P = 0.003) after adjustment for confounders. Our results show that plasma IL-18 was associated with HOMA-IR independent of obesity and type 2 diabetes.
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PMID:Elevated plasma interleukin-18 is a marker of insulin-resistance in type 2 diabetic and non-diabetic humans. 1611 17

Obesity and its associated disorders are increasing in companion animals, particularly in dogs. We have investigated whether genes encoding key adipokines, some of which are implicated in the pathologies linked to obesity, are expressed in canine adipose tissues. Using RT-PCR, mRNAs encoding the following adipokines were detected in dog white adipose tissue: adiponectin, leptin, angiotensinogen, plasminogen activator inhibitor-1, IL-6, haptoglobin, metallothionein-1 and 2, and nerve growth factor. The adipokine mRNAs were present in all fat depots examined. Fractionation of adipose tissue by collagenase digestion showed that each gene was expressed in mature adipocytes. The mRNA for TNFalpha was not evident in adipose tissue, but was detected in isolated adipocytes. Fibroblastic preadipocytes from gonadal white fat were differentiated into adipocytes in primary culture and adipokine expression examined before and after differentiation (days 0 and 11, respectively). Each adipokine gene expressed in dog white adipocytes was also expressed in the differentiated cells. These results demonstrate that dog white adipose tissue expresses major adipokine genes, expression being in the adipocytes. Investigation of adipokine production and function will provide insight into the mechanisms involved in obesity-related pathologies in dogs and serve as a model for the related human diseases.
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PMID:Adipokine gene expression in dog adipose tissues and dog white adipocytes differentiated in primary culture. 1613 59

Maturing Sprague-Dawley (S-D) rats develop obesity and skeletal muscle insulin resistance. To investigate the relationship between fat mass and insulin responses, we performed surgical removal of the epididymal and retroperitoneal depots of visceral adipose tissue (VF) or sham surgery (SHAM) in male rats aged 4 months. At sacrifice, 30 days later, the mass of visceral fat was 48% lower (p<0.05) in VF- compared to SHAM, while subcutaneous fat was essentially unchanged. VF- animals displayed increased insulin responses in isolated strips of skeletal muscle. Insulin-stimulated glucose transport was increased 28% in soleus muscle (p<0.05), with a trend toward a 31% increase in extensor digitorum longus muscle (p=0.058). Glucose tolerance was not significantly affected by surgical fat removal. In VF- animals, serum resistin was reduced 26% (p<0.05) and serum adiponectin was reduced 30% (p<0.05), with trends for reductions in IL-4 (58% reduction, p=0.084) and IL-6 (56% reduction, p=0.123). TNF-alpha, leptin and free fatty acids (NEFAs) were unchanged. We conclude that in maturing S-D rats, increased visceral adiposity leads to an increase in systemic release in resistin and possibly interleukins. Elevation of circulating cytokines may play a role in the development of muscle insulin resistance.
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PMID:Association of resistin with visceral fat and muscle insulin resistance. 1615 59


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