The gp130 Receptor Cytokine Family: Regulators of Adipocyte Development and Function

White, Ursula; Stephens, Jacqueline M.

doi:10.2174/138161211795164202

Cited by 75 publications

(61 citation statements)

References 121 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The current findings suggest that the IL-6 signaling-mediated increase in lipolysis is restricted to the portally drained mesenteric AT depot because depletion of gp130, the common signal transducer of IL-6, reduced FFA release only from isolated mesenteric but not from epididymal adipocytes. Because IL-6 is the gp130 cytokine with the best-known lipolytic function (9), this finding may be explained by an increased sensitivity of mesenteric adipocytes to IL-6-mediated lipolysis. However, IL-6-induced FFA release was only slightly elevated in mesenteric compared with epididymal adipocytes isolated from wild-type mice (1.25 6 0.14-fold in mesenteric vs. 1.12 6 0.02-fold in epididymal, P = 0.4).…”

Section: Discussionmentioning

confidence: 99%

“…Several IL-6 cytokines were shown to individually affect differentiation and adipogenesis, rendering gp130 a potential therapeutic target to combat obesity and its associated diseases (9). Accordingly, it was recently shown that blocking IL-6 transsignaling using a soluble gp130 Fc protein reduces obesityinduced infiltration of macrophages into AT (48).…”

Section: Discussionmentioning

confidence: 99%

“…In turn, this ligand/receptor complex associates with a homodimer of glycoprotein 130 (gp130), which is a common signal transducer protein of all IL-6 cytokines (8,9). Subsequently, the Janus kinase/signal transducer and activator transcription and extracellular signalrelated kinase (ERK) 1/2 pathways are activated (9,10).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Mesenteric Fat Lipolysis Mediates Obesity-Associated Hepatic Steatosis and Insulin Resistance

et al. 2015

View full text Add to dashboard Cite

Hepatic steatosis and insulin resistance are among the most prevalent metabolic disorders and are tightly associated with obesity and type 2 diabetes. However, the underlying mechanisms linking obesity to hepatic lipid accumulation and insulin resistance are incompletely understood. Glycoprotein 130 (gp130) is the common signal transducer of all interleukin 6 (IL-6) cytokines. We provide evidence that gp130-mediated adipose tissue lipolysis promotes hepatic steatosis and insulin resistance. In obese mice, adipocyte-specific gp130 deletion reduced basal lipolysis and enhanced insulin's ability to suppress lipolysis from mesenteric but not epididymal adipocytes. Consistently, free fatty acid levels were reduced in portal but not in systemic circulation of obese knockout mice. Of note, adipocyte-specific gp130 knockout mice were protected from high-fat diet-induced hepatic steatosis as well as from insulin resistance. In humans, omental but not subcutaneous IL-6 mRNA expression correlated positively with liver lipid accumulation (r = 0.31, P < 0.05) and negatively with hyperinsulinemic-euglycemic clamp glucose infusion rate (r = 20.28, P < 0.05). The results show that IL-6 cytokineinduced lipolysis may be restricted to mesenteric white adipose tissue and that it contributes to hepatic insulin resistance and steatosis. Therefore, blocking IL-6 cytokine signaling in (mesenteric) adipocytes may be a novel approach to blunting detrimental fat-liver crosstalk in obesity.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mesenteric Fat Lipolysis Mediates Obesity-Associated Hepatic Steatosis and Insulin Resistance

et al. 2015

View full text Add to dashboard Cite

show abstract

“…40 Interleukin-6 is considered to be an important inflammatory cytokine, specifically in autoimmune diseases, such as experimental autoimmune encephalomyelitis and rheumatoid arthritis. 41,42 This property may indicate the molecular pathway used by ES to upregulate the molecules observed in this study.…”

Section: Discussionmentioning

confidence: 99%

Endostatin gene therapy stimulates upregulation of ICAM-1 and VCAM-1 in a metastatic renal cell carcinoma model

et al. 2012

View full text Add to dashboard Cite

One of the greatest challenges in urological oncology is renal cell carcinoma (RCC), which is the third leading cause of death in genitourinary cancers. RCCs are highly vascularized and respond positively to antiangiogenic therapy. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we examined the potential of ES-based antiangiogenic therapy to activate tumor-associated endothelial cells in metastatic RCC (mRCC). Balb/c-bearing Renca cells were treated with NIH/3T3-LendSN or, as a control, with NIH/3T3-LXSN cells. The T-cell subsets and lymphocyte populations of tumors, mediastinal lymph nodes and the spleen were assessed by flow cytometry. The expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was assessed by real-time PCR, flow cytometry and immunohistochemistry analysis. ES gene therapy led to an increase in the percentage of infiltrating CD4-interferon (IFN)-g cells (Po0.05), CD8-IFN-g cells (Po0.01) and CD49b-tumor necrosis factor-a cells (Po0.01). In addition, ES therapy caused an increase at the mRNA level of ICAM-1 (1.4-fold; Po0.01) and VCAM-1 (1.5-fold) (control vs treated group; Po0.001). Through flow cytometry, we found a significant increase in the CD34/ICAM-1 cells (8.1-fold; Po0.001) and CD34/VCAM-1 cells (1.6-fold; Po0.05). ES gene therapy induced a significant increase in both T CD4 and CD8 cells in the lymph nodes and the spleen, suggesting that ES therapy may facilitate cell survival or clonal expansion. CD49b cells were also present in increased quantities in all of these organs. In this study, we demonstrate an antitumor inflammatory effect of ES in an mRCC model, and this effect is mediated by an increase in ICAM-1 and VCAM-1 expression in tumor-associated endothelial cells.

show abstract

“…CT-1 has been shown to regenerate cirrhotic livers and to improve steatosis in non-alcoholic fatty liver disease (NAFLD) (López-Yoldi et al, 2015). At least the three cytokines neuropoietin (NP), IL-11 and OSM have been shown to inhibit adipocyte differentiation (White and Stephens, 2011).…”

Section: Metabolic Actions Of Gp130 Ligandsmentioning

confidence: 99%

The role of gp130 receptor cytokines in the regulation of metabolic homeostasis

Cron

Allen

Febbraio

2016

Journal of Experimental Biology

View full text Add to dashboard Cite

It is well known that obesity is responsible, at least in part, for the increased incidence of chronic diseases such as type 2 diabetes, cardiovascular disease and certain types of cancer. Despite public education programs emphasizing lifestyle modifications to arrest this global pandemic, it is now estimated that 10-15% of the world's population are overweight or obese. As a result, new therapeutic options for the treatment of obesity-related disorders are clearly warranted. Much of the benefit of physical activity has been attributed to several mechanisms including reduced adiposity, increased cardiorespiratory fitness, reduced circulating lipids and the maintenance of muscle mass. However, the observation that the gp130 receptor cytokine interleukin-6 (IL-6) was released from skeletal muscle during exercise to improve metabolic homeostasis altered our understanding of the health benefits of exercise and opened avenues for research into potential novel therapeutics to treat metabolic disease. One gp130 receptor cytokine in particular, ciliary neurotrophic factor (CNTF), a pluripotent neurocytokine, showed efficacy as a potential anti-obesogenic therapy. This review examines the potential of gp130 receptor ligands, with a focus on IL-6 and CNTF as therapeutic strategies to treat obesity-related disorders.

show abstract

The gp130 Receptor Cytokine Family: Regulators of Adipocyte Development and Function

Cited by 75 publications

References 121 publications

Mesenteric Fat Lipolysis Mediates Obesity-Associated Hepatic Steatosis and Insulin Resistance

Mesenteric Fat Lipolysis Mediates Obesity-Associated Hepatic Steatosis and Insulin Resistance

Endostatin gene therapy stimulates upregulation of ICAM-1 and VCAM-1 in a metastatic renal cell carcinoma model

The role of gp130 receptor cytokines in the regulation of metabolic homeostasis

Contact Info

Product

Resources

About