The Inflammatory Syndrome: The Role of Adipose Tissue Cytokines in Metabolic Disorders Linked to Obesity

Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Harborview Medical Center, University of Washington, Seattle, Washington 98104-2499, USA. <>
Journal of the American Society of Nephrology (Impact Factor: 9.34). 12/2004; 15(11):2792-800. DOI: 10.1097/01.ASN.0000141966.69934.21
Source: PubMed


The metabolic effects of obesity have made this highly prevalent disease one of the most common risk factors for diabetes, hypertension, and atherosclerosis, the leading causes of end-stage renal failure. However, obesity per se, as defined by body mass index, is less predictive of the development of these diseases than is the presence of a constellation of obesity-related abnormalities now known as the metabolic syndrome. Recognition of this syndrome, which can readily be identified in clinical settings using defined threshold values for waist circumference, BP, fasting glucose, and dyslipidemia, allows for earlier intervention in these high-risk patients. Systemic insulin resistance has been implicated as one possible factor that links visceral obesity to adverse metabolic consequences; however, the mechanism whereby adipose tissue causes alterations in insulin sensitivity remains unclear. Infection and inflammation are commonly associated with insulin resistance, and visceral obesity is associated with a chronic, low-grade inflammatory state, suggesting that inflammation may be a potential mechanism whereby obesity leads to insulin resistance. Moreover, adipose tissue is now recognized as an immune organ that secretes numerous immunomodulatory factors and seems to be a significant source of inflammatory signals known to cause insulin resistance. Therefore, inflammation within white adipose tissue may be a crucial step contributing to the emergence of many of the pathologic features that characterize the metabolic syndrome and result in diabetes and atherosclerosis. This review describes the role of proinflammatory cytokines and hormones released by adipose tissue in generating the chronic inflammatory profile associated with visceral obesity.

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    • "UMAN AND RODENT studies indicate that acute and chronic alcohol consumption disrupts intestinal permeability, which increases leakage of various macromolecules including endotoxins such as lipopolysaccharide (LPS) (Lambert et al., 2003; Mathurin et al., 2000; Parlesak et al., 2000) and thus promotes subclinical inflammation. Subclinical chronic inflammation has been identified as a significant contributor to insulin resistance (Adachi et al., 1995; Lambert et al., 2003; Lindtner et al., 2013), and more specifically, local inflammation of adipose tissue may be the sentinel event that causes systemic insulin resistance and inflammation (Smith, 2002; Wisse, 2004). Adipose tissue inflammation is also associated with decreased levels of adiponectin, an adipokine with insulin-sensitizing and anti-inflammatory properties, and increased levels of visfatin, a visceral fatderived adipokine that has been shown to positively correlate with type II diabetes (Adeghate, 2008; Li et al., 2010). "
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    ABSTRACT: Background The digestive tract lymphatics transport approximately two-thirds of all lymph produced in the body and have a key role in mucosal immunity through their contribution to antigen transport and immune cell trafficking. Mesenteric lymphatic pumping function integrity is critical for maintaining homeostasis and lipid transport. We previously demonstrated that acute alcohol intoxication (AAI) increases mesenteric lymphatic amplitude of contraction and ejection fraction, enhancing the ability of the lymphatic vessels to pump lymph. AAI has been shown to disrupt intestinal barrier integrity, which would be expected to increase the endotoxin content of mesenteric lymph. In this study, we tested the prediction that AAI increases lymphatic permeability directly affecting perilymphatic adipose tissue (PLAT) milieu.Methods Male Sprague Dawley rats received an intragastric infusion of 2.5 g/kg of alcohol. Isovolumic administration of water (vehicle) served as control. PLAT was isolated for the determination of Evans Blue extravasation (permeability), cytokine content, and immunohistochemistry for inflammatory cell infiltration at 30 minutes and 24 hours after alcohol administration.ResultsPLAT isolated from AAI animals had greater Evans Blue concentrations and cytokine expression (24 hours post-AAI) and mast cell and neutrophil density than that isolated from controls. AAI resulted in significantly higher plasma lipopolysaccharide (endotoxin) levels, lower plasma adiponectin levels (at 30 minutes), and unchanged plasma visfatin levels.Conclusions The data indicate that AAI induces mesenteric lymphatic hyperpermeability, promotes PLAT inflammatory milieu and disrupts the systemic adipokine profile. These findings suggest an association between alcohol-induced lymphatic hyperpermeability and early manifestations of metabolic dysfunction as a result of alcohol abuse. We propose that crosstalk between lymph and PLAT results in adipose inflammation and adipokine dysregulation during AAI.
    Alcoholism Clinical and Experimental Research 07/2015; 39(8). DOI:10.1111/acer.12796 · 3.21 Impact Factor
    • "Assuming that environmental and lifestyle factors, BMI in particular, play a greater role in accounting for IL-6, we predicted that ICCs between the actual MZ co-twins would be no higher than for control adults who were closely matched on age, gender, BMI and a socio-economic index (SEI). By matching control subjects to the twin cases on these attributes, we simulated 4 of the major environmental and host factors known to influence IL-6 (Ershler and Keller, 2000; Friedman et al., 2005; Hjelmborg et al., 2008; Johnson and Krueger, 2005; O'Connor et al., 2007; Wisse, 2004). Hence, we could infer whether BMI and demographics (i.e., age, gender and SEI) accounted for the concordance between matched controls and co-twins. "
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    ABSTRACT: Interleukin-6 and C-reactive protein are commonly assessed biomarkers linked to illness, obesity, and stressful life events. However, relatively little is known about their heritability. By comparing Caucasian twins from the Midlife in the US project (MIDUS), we estimated the heritability of IL-6, its soluble receptor, and CRP. Based on the hypothesis that adiposity might contribute more to IL-6 than to sIL-6r, we fit heritability models quantifying the extent to which each reflected genetic and environmental factors shared with obesity. Genetic influences on IL-6 and its receptor proved to be distinct. Further, the appearance of a heritable basis for IL-6 was mediated largely via shared paths with obesity. Supporting this conclusion, we confirmed that when unrelated adult controls are carefully matched to twin participants on BMI, age, gender and socioeconomic indices, their IL-6 is similar to the corresponding twins. In contrast, the effect of BMI on CRP was split between shared genetics and environmental influences. In conclusion, IL-6 is strongly affected by factors associated with obesity accounting for its lability and responsiveness to diet, life style and contemporaneous events. Copyright © 2015. Published by Elsevier Inc.
    Brain Behavior and Immunity 06/2015; 49. DOI:10.1016/j.bbi.2015.05.010 · 5.89 Impact Factor
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    • "Weight loss, especially fat loss, in the postpartum phase has important health consequences. Accumulating evidence from recent studies points to the role of proinflammatory cytokines released by fat tissue in generating the chronic inflammatory profile associated with obesity and its related metabolic disorders [30]. Obesity-associated insulin resistance is thought to result, at least in part, from chronic subclinical inflammation [31]. "
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    ABSTRACT: Weight gain during the childbearing years and failure to lose pregnancy weight after birth contribute to the development of obesity in postpartum Latinas. Madres para la Salud [Mothers for Health] was a 12-month, randomized controlled trial exploring a social support intervention with moderate-intensity physical activity (PA) seeking to effect changes in body fat, fat tissue inflammation, and depression symptoms in sedentary postpartum Latinas. This report describes the efficacy of the Madres intervention. The results show that while social support increased during the active intervention delivery, it declined to pre-intervention levels by the end of the intervention. There were significant achievements in aerobic and total steps across the 12 months of the intervention, and declines in body adiposity assessed with bioelectric impedance. Social support from family and friends mediated increases in aerobic PA resulting in decrease in percent body fat. Trial registration Identifier: NCT01908959.
    BMC Public Health 09/2014; 14(1):971. DOI:10.1186/1471-2458-14-971 · 2.26 Impact Factor
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