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

Resistin is a new adipokine expressed in mouse, rat and human adipose tissue. Resistin may be an important link between obesity and insulin resistance, though this controversial view is complicated by the discovery of multiple sites of resistin expression, including human macrophages, placenta and pancreas. In previous studies we demonstrated that the mouse hypothalamo-pituitary system was also a site of resistin production. Pituitary resistin is developmentally regulated, reduced in the ob/ob mouse and severely down-regulated by food deprivation (24 h). An unexpected finding was that hypothalamic resistin mRNA remained unaffected by fasting. The present experiments examined the localization and possible regulation of hypothalamic resistin protein. Using immunohistochemistry we observed a complex network of resistin+ fibres extending rostrally from the arcuate nucleus of the hypothalamus (ARC) to the preoptic area. Labelled cell bodies occurred only in the ARC and in a periventricular region of the dorsal hypothalamus. Hypothalamic resistin immunoreactivity (ir) was unaffected by fasting (48 h) or by a high fat diet, but the periventricular staining was greatly increased in the lactating mouse. Marked reductions in resistin+ fibres were seen in brain tissue from: (a) ob/ob mice, (b) young mice made underweight for their age by raising them in large litters (20 pups per litter) and (c) mice with hypothalamic lesions induced by monosodium glutamate (MSG) or gold thioglucose (GTG). We speculate that the resistin-ir deficit in genetically obese mice, and in severely underweight mice, could be due to low or absent leptin. In contrast, though MSG- and GTG-treated mice have high levels of circulating leptin, in the presence of excessive visceral fat deposits, we hypothesize that damage to the ARC destroys the resistin+ cell bodies. This latter supposition led us to an additional hypothesis, that resistin-ir would be contained in neurons expressing the proopiomelanocortin (POMC) gene. This proved to be correct. Double label immunofluorescence histochemistry revealed that alpha-MSH-ir, a marker for POMC neurons, was co-localized with resistin-ir. In conclusion, our data reveal a second example of an adipocytokine co-localized with a hypothalamic neuropeptide. We reported previously that leptin was co-localized with oxytocin and vasopressin. RT-PCR analysis confirmed that resistin mRNA is readily detectable in ARC, but further work is required to determine whether the resistin gene is expressed in POMC neurons or if resistin is specifically accumulated by these cells. Nonetheless, our data suggest that the hypothalamus is a target tissue for resistin.
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PMID:Hypothalamic resistin immunoreactivity is reduced by obesity in the mouse: co-localization with alpha-melanostimulating hormone. 1580 9

The adipokine resistin is suggested to be an important link between obesity and insulin resistance. In the present study, we assessed the impact of resistin as inflammatogenic cytokine in the setting of arthritis. In vitro experiments on human PBMC were performed to assess cytokine response and transcription pathways of resistin-induced inflammation. Proinflammatory properties of resistin were evaluated in animal model by intra-articular injection of resistin followed by histological evaluation of the joint. Levels of resistin were assessed by ELISA in 74 paired blood and synovial fluid samples of patients with rheumatoid arthritis. Results were compared with the control group comprised blood samples from 34 healthy individuals and 21 synovial fluids from patients with noninflammatory joint diseases. We now show that resistin displays potent proinflammatory properties by 1) strongly up-regulating IL-6 and TNF-alpha, 2) responding to TNF-alpha challenge, 3) enhancing its own activity by a positive feedback, and finally 4) inducing arthritis when injected into healthy mouse joints. Proinflammatory properties of resistin were abrogated by NF-kappaB inhibitor indicating the importance of NF-kappaB signaling pathway for resistin-induced inflammation. Resistin is also shown to specifically accumulate in the inflamed joints of patients with rheumatoid arthritis and its levels correlate with other markers of inflammation. Our results indicate that resistin is a new and important member of the cytokine family with potent regulatory functions. Importantly, the identified properties of resistin make it a novel and interesting therapeutic target in chronic inflammatory diseases such as rheumatoid arthritis.
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PMID:Resistin, an adipokine with potent proinflammatory properties. 1584 82

Polycystic ovary syndrome (PCOS) is associated with an increased incidence of insulin resistance (IR), obesity, and type 2 diabetes. Resistin, an adipocytokine, may represent a link between obesity, and these metabolic disorders. There is also evidence that inflammation is a hyperresistinemic state in humans, and cytokine induction of resistin may contribute to insulin resistance in endotoxemia, obesity, and other inflammatory states. In contrast, adiponectin, increases insulin sensitivity, improves glucose tolerance, inhibits inflammatory pathways, while adenovirus-expressed adiponectin reduces atherosclerotic lesions in a mouse model of atherosclerosis. We aimed to assess, in women with PCOS, whether there is a relationship between adiponectin and resistin and the indices of IR, and whether serum levels of these adipocytokines are altered by glucose-induced hyperinsulinaemia. Serum levels of resistin and adiponectin were measured at 0, 60, and 120 min during 75 g oral glucose tolerance test (OGTT), in 19 women with PCOS, age 36.3+/-11.4 years (mean+/-SD), body mass index (BMI) 29.3+/-7.7 kg/m2, and correlated with the indices of IR, such as HOMA-IR, QUICKI, and the insulin resistance index calculated from glucose and insulin levels obtained during OGTT. There was no change in resistin concentrations (7.31+/-4.58, 7.47+/-5.40, 7.22+/-5.12 pg/ml, at 0, 60, and 120 min of OGTT, respectively, P = 0.77), but there was an increase in adiponectin from 11.32+/-4.64 microg/ml at baseline to 14.78+/-7.41 microg/ml, at 120 min of OGTT (P < 0.01). The magnitude of the overall rise in adiponectin was greater from 60 to 120 min (from 12.31+/-5.72 to 14.78+/-7.41 microg/ml, P < 0.006). Neither resistin, nor adiponectin correlated with the indices of IR, lipids, or other hormonal parameters of the PCOS. There was, however, a significant negative correlation between serum resistin and adiponectin (P = 0.001). In conclusion, we observed a strong negative correlation between serum adiponectin and resistin, despite the lack of direct correlation with the indices of IR. Given the opposite effects of resistin and adiponectin on the inflammatory process, we speculate that relative proportion of adiponectin-to-resistin might potentially influence cardiometabolic risk in women with the PCOS independently of IR parameters. The observed increase in adiponectin during OGTT requires further study.
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PMID:Adiponectin and resistin serum levels in women with polycystic ovary syndrome during oral glucose tolerance test: a significant reciprocal correlation between adiponectin and resistin independent of insulin resistance indices. 1586 82

The role of resistin in human biology remains uncertain. We measured serum resistin levels in Japanese patients with (n=111) and without (n=98) type 2 diabetes mellitus and investigated the significance of this hormone in the pathophysiology of diabetes. The levels of serum adiponectin and leptin were also measured. Resistin levels were increased significantly in patients with type 2 diabetes compared with non-diabetic subjects (24.7+/-2.6 vs. 15.0+/-1.2 ng/ml, p=0.0013). However, there was no correlation in either patient group between serum resistin levels and markers of insulin resistance, obesity or hyperlipidaemia. These results were in direct contrast to the data of leptin or adiponectin, both of which were closely related to these clinical markers of diabetes. Multivariate regression analysis on the combined data of the two groups demonstrated that the presence of diabetes and HDL cholesterol levels were significant predictors of serum resistin levels (diabetes: beta=0.159, p=0.035; HDL: beta=-0.172, p=0.039). No correlation was observed between C-reactive protein and resistin adjusted for BMI. Taken together, these findings demonstrate that serum resistin levels are increased in patients with type 2 diabetes, but this increase is not linked to markers of insulin resistance or adiposity. Further studies are necessary to elucidate the significance of serum resistin concentration in human pathophysiology.
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PMID:Increased serum resistin levels in patients with type 2 diabetes are not linked with markers of insulin resistance and adiposity. 1594 45

Resistin, a recently discovered 92 amino acid protein involved in the development of insulin resistance, has been associated with obesity and type 2 diabetes. The elevated serum resistin in human diabetes is often associated with a pro-inflammatory milieu. However, the role of resistin in the development of inflammation is not well understood. Addition of recombinant human resistin protein (hResistin) to macrophages (both murine and human) resulted in enhanced secretion of pro-inflammatory cytokines, TNF-alpha and IL-12, similar to that obtained using 5 microg/ml lipopolysaccharide. Both oligomeric and dimeric forms of hResistin were able to activate these cytokines suggesting that the inflammatory action of resistin is independent of its conformation. Heat denatured hResistin abrogated cytokine induction while treatment of recombinant resistin with polymyxin B agarose beads had no effect thereby ruling out the role of endotoxin in the recombinant hResistin mediated cytokine induction. The pro-inflammatory nature of hResistin was further evident from the ability of this protein to induce the nuclear translocation of NF-kappaB transcription factor as seen from electrophoretic mobility shift assays. Induction of TNF-alpha in U937 cells by hResistin was markedly reduced in the presence of either dominant negative IkappaBalpha plasmid or PDTC, a pharmacological inhibitor of NF-kappaB. A protein involved in conferring insulin resistance is also a pro-inflammatory molecule that has important implications.
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PMID:Human resistin stimulates the pro-inflammatory cytokines TNF-alpha and IL-12 in macrophages by NF-kappaB-dependent pathway. 1603 94

Resistin is a member of a class of cysteine-rich proteins collectively termed resistin-like molecules. Resistin has been implicated in the pathogenesis of obesity-mediated insulin resistance and T2DM (Type II diabetes mellitus), at least in rodent models. In addition, resistin also appears to be a pro-inflammatory cytokine. Taken together, resistin, like many other adipocytokines, may possess a dual role in contributing to disease risk. However, to date there has been considerable controversy surrounding this 12.5 kDa polypeptide in understanding its physiological relevance in both human and rodent systems. Furthermore, this has led some to question whether resistin represents an important pathogenic factor in the aetiology of T2DM and cardiovascular disease. Although researchers still remain divided as to the role of resistin, this review will place available data on resistin in the context of our current knowledge of the pathogenesis of obesity-mediated diabetes, and discuss key controversies and developments.
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PMID:Role of resistin in obesity, insulin resistance and Type II diabetes. 1610 44

Resistin has been postulated to play a role in obesity-related insulin resistance. To explore this possibility, we have investigated effects of acute euglycemic (5.2+/-0.1 mmol/L) hyperinsulinemia (96+/-8 microU/mL) with and without concurrent infusion of lipid plus heparin (to raise or lower plasma free fatty acid [FFA] levels) on glucose turnover and plasma resistin levels in alert rats. Plasma FFA concentrations increased during lipid/heparin (L/H) infusion (from 0.82 to 2.86 mmol/L, P<.001) and decreased (from 0.83 to 0.21 mmol/L, P<.001) in controls who were infused with insulin but not with L/H. L/H infusion reduced insulin suppression of endogenous glucose production by approximately 90% (from 28.9 to 3.1 mg. kg-1 . min-1, P<.001) and insulin-stimulated glucose uptake (glucose rate of disappearance) by 78% (from 30.8% to 6.9%, P<.001). Plasma resistin levels increased by 46% (from 39.9 to 58.4 microg/L, P<.05) during L/H infusion and did not change in controls (39.7 vs 39.3 microg/L). Plasma ghrelin levels decreased by 41% (from 892 to 584 ng/L, P<.05) in response to hyperinsulinemia, whereas concurrent L/H infusion had no additional effect on ghrelin levels (584+/-67 vs 548+/-82 ng/L). In summary, we found that FFA induced hepatic insulin resistance, and to a lesser extent, peripheral insulin resistance was associated with elevated plasma resistin levels. We conclude that FFA-induced release of resistin may contribute to the development of FFA-induced insulin resistance in rats.
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PMID:Effects of free fatty acids on plasma resistin and insulin resistance in awake rats. 1612 24

Resistin has been proposed as a potential link between obesity and insulin resistance. It is also well established that altered metabolism of fatty acids by skeletal muscle can lead to insulin resistance and lipotoxicity. However, little is known about the effect of resistin on long chain fatty acid uptake and metabolism in skeletal muscle. Here we show that treating rat skeletal muscle cells with recombinant resistin (50 nM, 24 h) decreased uptake of palmitate. This correlated with reduced cell surface CD36 content and lower expression of FATP1, but no change in FATP4 or CD36 expression. We also found that resistin decreased fatty acid oxidation by measuring 14CO2 production from [1-14C] oleate and an increase in intracellular lipid accumulation was detected in response to resistin. Decreased AMPK and ACC phosphorylation were observed in response to resistin while expression of ACC and AMPK isoforms was unaltered. Resistin mediated these effects without altering cell viability. In summary, our results demonstrate that chronic incubation of skeletal muscle cells with resistin decreased fatty acid uptake and metabolism via a mechanism involving decreased cell surface CD36 content, FATP1 expression and a decrease in phosphorylation of AMPK and ACC.
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PMID:Regulation of fatty acid uptake and metabolism in L6 skeletal muscle cells by resistin. 1613 86

Resistin, an adipocyte-derived cytokine linked to insulin resistance and obesity, has recently been shown to activate endothelial cells (ECs). Using microarrays, we found that along with numerous other pro-atherosclerotic genes, resistin expression levels are elevated in the aortas of C57BL/6J apoE-/- mice; these findings led us to further explore the relation between resistin and atherosclerosis. Using TaqMan PCR and immunohistochemistry, we found that ApoE-/- mice had significantly higher resistin mRNA and protein levels in their aortas, and elevated serum resistin levels, compared to C57BL/6J wild-type mice. Incubation of murine aortic ECs with recombinant resistin increased monocyte chemoattractant protein (MCP)-1 and soluble vascular cell adhesion molecule (sVCAM)-1 protein levels in the conditioned medium. Furthermore, human carotid endarterectomy samples stained positive for resistin protein, while internal mammary artery did not show strong staining. Patients diagnosed with premature coronary artery disease (PCAD) were found to have higher serum levels of resistin than normal controls. In summary, resistin protein is present in both murine and human atherosclerotic lesions, and mRNA levels progressively increase in the aortas of mice developing atherosclerosis. Resistin induces increases in MCP-1 and sVCAM-1 expression in murine vascular endothelial cells, suggesting a possible mechanism by which resistin might contribute to atherogenesis. Finally, PCAD patients exhibited increased serum levels of resistin when compared to controls. These findings suggest a possible role of resistin in cardiovascular disease.
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PMID:The potential role of resistin in atherogenesis. 1615 96

Resistin and adiponectin are adipokines with postulated opposite functions. Resistin has been related with insulin resistance in obesity, while adiponectin could be associated to higher insulin sensitivity. We have determined whether the production of these two adipokines during the day is related to the feeding rhythm in rats. Resistin mRNA levels in adipose tissue correlated positively with the gastric contents and serum insulin concentration, showing higher levels during the dark phase (period of the highest food intake), especially in the mesenteric depot, while levels decreased during the light phase. The diurnal pattern of resistin expression was not directly reflected in the circulating levels, but it showed a 6-h delay and correlated negatively with the gastric contents and serum insulin. Adiponectin expression followed an opposite pattern, not apparently related to feeding or insulin release, and not translated into changes in circulating levels. Moreover, considering that insulin stimulates resistin expression and that circulating resistin follows a contrary circadian pattern in comparison to insulin, resistin, apart from its role in the increased insulin resistance associated to obesity, could also act as a putative modulator of insulin in the daily feeding/fasting rhythm through a negative feedback regulation of its action.
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PMID:Resistin as a putative modulator of insulin action in the daily feeding/fasting rhythm. 1640 8


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