Human resistin: found in translation from mouse to man.

Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Trends in Endocrinology and Metabolism (Impact Factor: 8.87). 04/2011; 22(7):259-65. DOI: 10.1016/j.tem.2011.03.005
Source: PubMed

ABSTRACT The discovery of resistin 10 years ago as a fat cell-secreted factor that modulates insulin resistance suggested a link to the current obesity-associated epidemics of diabetes and cardiovascular disease, which are major human health concerns. Although adipocyte-derived resistin is indisputably linked to insulin resistance in rodent models, the relevance of human resistin is complicated because human resistin is secreted by macrophages rather than adipocytes, and because of the descriptive nature of human epidemiology. In this review, we examine the recent and growing evidence that human resistin is an inflammatory biomarker and a potential mediator of diabetes and cardiovascular disease.

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    ABSTRACT: The association between adipokines and inflammatory periodontal diseases has been studied over the last two decades. This review was intended to explore the observation that periodontal therapy may lead to an improvement of adipokines in diabetic patients. In summary, substantial evidence suggests that diabetes is associated with increased prevalence, extent and severity of periodontitis. Numerous mechanisms have been elucidated to explain the impact of diabetes on the periodontium. However, current knowledge concerning the role of major adipokines indicates only some of their associations with the pathogenesis of periodontitis in type 2 diabetes. Conversely, treatment of periodontal disease and reduction of oral inflammation may have positive effects on the diabetic condition, although evidence for this remains somewhat equivocal.
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    ABSTRACT: Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that also plays a regulatory role in fat metabolism. In 3T3-L1 cells, resistin was demonstrated to be a key mediator of GIP stimulation of lipoprotein lipase (LPL) activity, involving activation of protein kinase B (PKB) and reduced phosphorylation of liver kinase B1 (LKB1) and AMP-activated protein kinase (AMPK). The current study was initiated to determine whether resistin has additional roles in GIP-regulated adipocyte functions. Analysis of primary adipocytes isolated from Retn−/−, Retn+/−, and Retn+/+ mice found that GIP stimulated the PKB/LKB1/AMPK/LPL pathway and fatty acid uptake only in Retn+/+ adipocytes, suggesting that GIP signaling and/or GIP responsiveness were compromised in Retn+/− and Retn−/− adipocytes. GIP receptor (GIPR) protein and mRNA were decreased in Retn+/− and Retn−/− adipocytes, but resistin treatment rescued LPL responsiveness to GIP. In addition, genes encoding tumor necrosis factor (TNF), TNF receptor 2 (TNFR2), and the signaling proteins stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK), were downregulated, and phosphorylated levels of SAPK/JNK/c-Jun were decreased in Retn−/− mice. Chromatin immunoprecipitation assays were used to identify a 12-O-tetradecanoylphorbol-13-acetate (TPA)-response element (TRE-III) responsible for c-Jun–mediated transcriptional activation of Gipr. Blunted GIP responsiveness in Retn+/− and Retn−/− adipocytes was therefore largely due to the greatly reduced GIPR expression associated with decreased c-Jun–mediated transcriptional activation of Gipr.
    Diabetes 01/2012; 62(2):471-477. DOI:10.2337/db12-0257 · 8.47 Impact Factor
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    ABSTRACT: Objective: To describe the relationship between circulating resistin levels and cardiovascular diseases (CVD) and all-cause death in a multi-ethnic cohort. Methods and results: We studied 1913 participants from the Multi-Ethnic Study of Atherosclerosis with measurements of plasma resistin levels. Absolute proportions experiencing new-onset atrial fibrillation (AF), atherosclerotic CVD (myocardial infarction, angina, resuscitated cardiac arrest, stroke), heart failure (HF), and all-cause death were calculated for each quartile of resistin. We used adjusted Cox proportional regression modeling resistin as a continuous variable per standard deviation of log-transformed resistin and secondarily as a categorical variable using resistin quartiles. Results were stratified by sex and race/ethnicity. The mean age of the population was 64.5 ± 10 years with half being female and a median resistin concentration of 15.1 ng/mL (11.9-19.1). Mean follow-up time was 7.2 ± 1.8 years. There was a graded increase in the occurrence of all outcomes across increasing quartiles of resistin. Modeled as a continuous variable, after adjustment for anthropomorphic measures, traditional risk factors, markers of inflammation, and other adipokines, significant associations were noted for HF (HR 1.4, CI 1.0-2.0), hard and all CVD (HR 1.3, 1.1-1.7 and 1.3, 1.1-1.6, respectively), and CHD (HR 1.31, 1.0-1.6), but not for AF or death. Significant interaction terms were noted between resistin and race, with Hispanic race/ethnicity showing the strongest relationship between resistin and outcomes. Conclusions: In an ethnically diverse population without known CVD at baseline, there was a strong, independent association between higher resistin levels and incident CVD, CHD and HF. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Atherosclerosis 12/2014; 239(1):101-108. DOI:10.1016/j.atherosclerosis.2014.12.044 · 3.97 Impact Factor


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