Expression of Interleukin-6 Is Greater in Preadipocytes than in Adipocytes of 3T3-L1 Cells and C57BL/6J and ob/ob Mice

Harkins, Janette M.; Moustaid‐Moussa, Naima; Chung, Yunro; Penner, Kristen M.; Pestka, James J.; North, Colin M.; Claycombe, Kate J.

doi:10.1093/jn/134.10.2673

Cited by 148 publications

(118 citation statements)

References 27 publications

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“…As previously reported [1], we confirmed the increased expression of Tnf in the WAT from mice with diet-induced obesity, while no alteration of Il6 expression was found. This is in contrast to the previously reported overexpression of Il6 in the WAT of genetically obese ob/ob mice [28], which, however, have a much more pronounced increase in fat mass than our model of diet-induced obesity.…”

Section: Discussioncontrasting

confidence: 99%

Interleukin-1 receptor antagonist is upregulated during diet-induced obesity and regulates insulin sensitivity in rodents

et al. 2005

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Aims/hypothesis: The IL-1 receptor antagonist (IL-1Ra) is an anti-inflammatory cytokine known to antagonise the actions of IL-1. We have previously shown that IL-1Ra is markedly upregulated in the serum of obese patients, is correlated with BMI and insulin resistance, and is overexpressed in the white adipose tissue (WAT) of obese humans. The aim of this study was to examine the role of IL-1Ra in the regulation of glucose homeostasis in rodents. Methods: We assessed the expression of genes related to IL-1 signalling in the WAT of mice fed a high-fat diet, as well as the effect of Il1rn (the gene for IL-1Ra) deletion and treatment with IL-1Ra on glucose homeostasis in rodents. Results: We show that the expression of Il1rn and the gene encoding the inhibitory type II IL-1 receptor was upregulated in diet-induced obesity. The blood insulin:glucose ratio was significantly lower in Il1rn −/− animals, which is compatible with an increased sensitivity to insulin, reinforced by the fact that the insulin content and pancreatic islet morphology of Il1rn −/− animals were normal. In contrast, the administration of IL-1Ra to normal rats for 5 days led to a decrease in the whole-body glucose disposal due to a selective decrease in muscle-specific glucose uptake. Conclusions/interpretation: The expression of genes encoding inhibitors of IL-1 signalling is upregulated in the WAT of mice with diet-induced obesity, and IL-1Ra reduces insulin sensitivity in rats through a muscle-specific decrease in glucose uptake. These results suggest that the markedly increased levels of IL-1Ra in human obesity might contribute to the development of insulin resistance.

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Section: Discussioncontrasting

confidence: 99%

Interleukin-1 receptor antagonist is upregulated during diet-induced obesity and regulates insulin sensitivity in rodents

et al. 2005

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“…Others already suggested differences in the capacity of adipokine production by pre-adipocytes compared to mature adipocytes. [52][53][54] We demonstrated that adiponectin was mainly produced by adipocytes, while IL-6 and PAI were produced by both adipocytes and pre-adipocytes, but pre-adipocytes produced more IL-6 and PAI than adipocytes.…”

Section: Discussionmentioning

confidence: 79%

Infection-induced inflammatory response of adipocytes in vitro

et al. 2008

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Background: Abdominal obesity plays an important role in the development of insulin resistance, diabetes mellitus and atherosclerosis. The exact pathophysiological mechanisms are unclear but adipocyte dysfunction is thought to be crucial. Infections are associated with the development of atherosclerosis as well as diabetes. In this study we investigated whether adipocytes can be infected and whether this results in production of inflammatory cytokines relevant for the development of atherosclerosis and diabetes. Methods: Pre-adipocytes were cultured and differentiated into mature adipocytes in vitro. Adipocytes and pre-adipocytes were incubated with infective and heat-inactivated Chlamydia pneumoniae, cytomegalovirus (CMV), adenovirus (Ad) subtypes 2 and 36, influenza A and respiratory syncitial virus (RSV). After 48 h, adiponectin, interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a) and plasminogen activator inhibitor-1 (PAI-1) were measured in supernatants. Results: Infection of adipocytes with Ad-36, CMV and RSV resulted in increased IL-6 production from 192 ± 22 pg ml À1 (uninfected) to 1030 ± 86 pg ml À1 , 838 ± 59 pg ml À1 and 1241 ± 191 pg ml À1 , respectively (all Po0.01 vs control). In addition, Ad-36 infection slightly reduced PAI production in adipocytes (285 ± 26.8 ng ml À1 vs uninfected: 477 ± 71.2 ng ml À1 ; P ¼ 0.05) and pre-adipocytes (709±43.3 ng ml À1 vs uninfected: 1071±71.8 ng ml À1 ; Po0.01). In contrast, human Ad type 2 did not exert any effect on IL-6 or PAI production. None of the microorganisms induced significant changes in adiponectin and/or TNF-a production. Conclusions: Adipocytes can be infected with several microorganisms in vitro. Infection of adipocytes with Ad-36, but not Ad-2 leads to increased production of IL-6 which might contribute to chronic low-grade inflammation, a process known to be involved in the development of cardiovascular diseases and type 2 diabetes.

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“…Based on immunoselective isolation of cell fractions, they suggest that the major contributors of CXCL5 in adipose tissue are macrophages present in the stromal vascular fraction. However, the use of IL-6 and MCP-1 as specific markers for macrophages in the selection process is misleading because these proteins are also highly expressed in preadipocytes (29,41). Therefore, the relative contribution of macrophages and preadipocytes to both CXCL5 and KC expression by the stromal vascular fraction deserves further study.…”

Section: Discussionmentioning

confidence: 99%

Keratinocyte-derived Chemokine in Obesity

Neels

Badeanlou

Hester

et al. 2009

Journal of Biological Chemistry

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Obese adipose tissue (AT) is associated with chronic inflammation, and we hypothesized that the keratinocyte-derived chemokine (KC), the mouse ortholog of human interleukin-8, plays a role in obesity-mediated AT inflammation and the subsequent manifestation of insulin resistance. KC expression is increased in the AT and plasma of genetically (ob/ob) and high fat dietinduced obese mouse models, and this increase may be mediated by the elevated leptin and tumor necrosis factor-␣ levels associated with obesity. Obesity-induced KC expression occurs primarily in stromal vascular cells and not in adipocytes, and it is high in preadipocytes and decreases during adipogenesis. Although KC has no effect on adipogenesis, it induces adipocyte expression of inflammatory factors and the insulin resistance mediator, suppressor of cytokine signaling 3. Using chimeric mice deficient in the KC receptor CXCR2 in their bone marrow, we show that the lack of CXCR2 in hematopoietic cells is sufficient to protect from adipose and skeletal muscle macrophage recruitment and development of insulin resistance in diet-induced obese mice. These studies suggest that KC and its receptor CXCR2 are potential targets for the development of new therapeutic approaches for treatment of obesity-related insulin resistance, type II diabetes, and related cardiovascular diseases.Obesity is characterized by systemic low grade inflammation that appears to contribute to the genesis of insulin resistance (IR), 3 type 2 diabetes, and increased risk for cardiovascular diseases (reviewed in Ref. 1). Furthermore, adipose tissue (AT) produces a variety of inflammatory factors, and its excessive development in obesity is associated with accumulation of AT macrophages (ATMs) (1), whose recruitment and proinflammatory activation are required for the development of IR in obese mice (reviewed in Ref. 2). An important question concerning ATMs is/are the trigger(s) driving the recruitment of these cells in obesity.Efforts at identifying factors that attract and recruit ATMs have mostly focused on the CC chemokine MCP-1 (monocyte chemoattractant protein-1) and its receptor CCR2. These studies have led to contradicting results with several publications showing that MCP-1 and CCR2 are important for ATM recruitment and the subsequent development of IR (3-5), whereas others show no involvement of this chemokine and its receptor in these processes (6 -8). Furthermore, the studies that claim a role for MCP-1 and CCR2 in ATM recruitment and IR show that deficiency of the ligand or the receptor did not result in normalization of ATM content, indicating that other factors also participate in ATM recruitment. These findings suggest that the precise role of the MCP-1/CCR2 axis in ATM recruitment and IR is unclear, and that other chemokines and their receptors could also play a role in these processes. One such chemokine is interleukin 8 (IL-8), the prototypical CXC chemokine known to recruit and activate monocytes and to attract polymorphonuclear leukocytes to sites of inflammation...

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Expression of Interleukin-6 Is Greater in Preadipocytes than in Adipocytes of 3T3-L1 Cells and C57BL/6J and ob/ob Mice

Cited by 148 publications

References 27 publications

Interleukin-1 receptor antagonist is upregulated during diet-induced obesity and regulates insulin sensitivity in rodents

Interleukin-1 receptor antagonist is upregulated during diet-induced obesity and regulates insulin sensitivity in rodents

Infection-induced inflammatory response of adipocytes in vitro

Keratinocyte-derived Chemokine in Obesity

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