Tumor Necrosis-Like Weak Inducer of Apoptosis as a Proinflammatory Cytokine in Human Adipocyte Cells: Up-Regulation in Severe Obesity Is Mediated by Inflammation But Not Hypoxia

Vendrell, Joan; Maymó-Masip, Elsa; Tinahones, Francisco J.; Garcı́a-España, Antonio; Megía, Ana; Caubet, Enric; Garcı́a-Fuentes, Eduardo; Chacón, Matilde R.

doi:10.1210/jc.2009-2481

Cited by 62 publications

(45 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Infl ammation is one of the mechanisms linking obesity, insulin resistance and other metabolic-related disturbances (Wisse, 2004). At the same time, only slight elevation of proinfl ammatory cytokines was observed in the obtained animal model being indicative that current dietary intervention did not induce systemic infl ammation that is observed in severe obesity (Vendrell et al, 2010). The obtained data on altered adipose tissue zinc content in HF-fed animals are in agreement with the previously published articles (Liu et al, 2013;Tallman and Taylor, 2003).…”

Section: Discussionsupporting

confidence: 89%

Decreased adipose tissue zinc content is associated with metabolic parameters in high fat fed Wistar rats

Tinkov

Popova

Gatiatulina

et al. 2016

Acta Sci Pol Technol Aliment

View full text Add to dashboard Cite

Background. Limited data on adipose tissue zinc content in obesity exist. At the same time, the association between adipose tissue zinc content and metabolic parameters in dietary-induced obesity is poorly studied. Therefore, the primary objective of this study is to assess adipose tissue zinc content and its association with morphometric parameters, adipokine spectrum, proinfl ammatory cytokines, and apolipoprotein profi le in high fat fed Wistar rats. Material and methods. A total of 48 adult female Wistar rats were used in the present study. Rats were fed either control (10% of fat) or high fat diet (31.6% of fat). Adipose tissue zinc content was assessed using inductively coupled plasma mass spectrometry. Rats' serum was examined for adiponectin, leptin, insulin, interleukin-6, and tumor necrosis factor-α using enzyme-linked immunosorbent assay kits. Serum glucose and apolipoprotein spectrum were also evaluated. Results. High fat feeding resulted in a signifi cant 34% decrease in adipose tissue zinc content in comparison to the control values. Fat pad zinc levels were signifi cantly inversely associated with morphometric parameters, circulating leptin, insulin, tumor necrosis factor-α levels and HOMA-IR values. At the same time, a signifi cant correlation with apolipoprotein A1 concentration was observed. Conclusion. Generally, the obtained data indicate that (1) high fat feeding results in decreased adipose tissue zinc content; (2) adipose tissue zinc content is tightly associated with excessive adiposity, infl ammation, insulin resistance and potentially atherogenic changes.

show abstract

Section: Discussionsupporting

confidence: 89%

Decreased adipose tissue zinc content is associated with metabolic parameters in high fat fed Wistar rats

Tinkov

Popova

Gatiatulina

et al. 2016

Acta Sci Pol Technol Aliment

View full text Add to dashboard Cite

show abstract

“…This observation emphasizes the differences that exist between cell types in transducing signals from common receptors, thereby mediating distinct biological functions. In line with this finding, it has now been established that the biological activity of TWEAK can be independent of NF-B and requires the activation of alternative cell signaling pathways such as ERK or p38 MAPK signaling (Ando et al, 2006;Sanz et al, 2009;Vendrell et al, 2010). We further demonstrated that ERK and p38 MAPK pathways are indispensable for TWEAK-dependent mitogenic function, a result compatible with the well known central role of these MAPKs in cell proliferation (Zhang and Liu, 2002).…”

Section: Discussionsupporting

confidence: 87%

Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Induces Astrocyte Proliferation through the Activation of Transforming-Growth Factor-α/Epidermal Growth Factor Receptor Signaling Pathway

Rousselet¹,

Traver

Monnet

et al. 2012

Mol Pharmacol

View full text Add to dashboard Cite

Reactive astrogliosis is beneficial in many aspects; however, it is also detrimental in some pathological states such as the development of lethal brain tumors. It is therefore crucial to understand the mechanisms regulating astrocyte proliferation. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor family, was shown to stimulate astrocyte proliferation in vitro. Herein, we further characterize the mitogenic potential of TWEAK on central nervous system cells. Among these cells, astrocytes express the highest level of TWEAK and Fn14 transcripts, suggesting that they are particularly sensitive to TWEAK stimulation. Using in vitro model systems, we found that TWEAK was as potent as epidermal growth factor (EGF) (a prototypical astrocyte mitogen) in mediating astrocyte proliferation.However, its mitogenic activity was delayed compared with that of EGF, suggesting distinct mechanisms of action. Using cell signaling pathway inhibitors, neutralizing antibodies, and protein assays, we further show that the mitogenic activity of TWEAK on primary astrocytes requires stimulation of the transforming growth factor-␣ (TGF-␣) and of the epidermal growth factor receptor (EGFR) signaling pathway through extracellular signal-regulated kinase and p38 mitogen-activated protein kinase activation. In aggregates, our data demonstrate that TWEAK acts as a potent astrocyte mitogen through the induction of a TGF-␣/EGFR signaling pathway. We anticipate that description of such a mechanism may allow novel approaches to human pathologies associated with astrocyte proliferation.

show abstract

“…However, the real contribution of each tissue to circulating sTWEAK is unknown. The low level of TWEAK mRNA detected in human adipose tissue (42) suggests that adipose tissue contribution to circulating sTWEAK circulation is minor. Interestingly, our unpublished findings suggest that circulating sTWEAK is negatively correlated with fat mass (under review).…”

Section: Discussionmentioning

confidence: 98%

“…Although TWEAK and its receptor Fn14 are expressed in a variety of organs, including adipose tissue (7), the physiological and patho-physiological roles of this cytokine in an obesity-associated insulin-resistant state remains largely unknown. TWEAK has been described to inhibit adipogenesis (40) and we have recently shown that TWEAK may have a proinflammatory function in human subcutaneous adipocytes (42). However, clinical studies have shown a negative association between † Deceased 7 April 2010.fasting glucose and soluble circulating sTWEAK levels, as well as a decrease of sTWEAK in patients with T2D (24).…”

mentioning

confidence: 99%

TWEAK prevents TNF-α-induced insulin resistance through PP2A activation in human adipocytes

Vázquez-Carballo

Ceperuelo-Mallafré

Chacón

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

View full text Add to dashboard Cite

show abstract

Tumor Necrosis-Like Weak Inducer of Apoptosis as a Proinflammatory Cytokine in Human Adipocyte Cells: Up-Regulation in Severe Obesity Is Mediated by Inflammation But Not Hypoxia

Abstract: Our data suggest that TWEAK acts as a pro-inflammatory cytokine in the adipose tissue and that inflammation, but not hypoxia, may be behind its up-regulation in severe obesity.

Cited by 62 publications

References 30 publications

Decreased adipose tissue zinc content is associated with metabolic parameters in high fat fed Wistar rats

Decreased adipose tissue zinc content is associated with metabolic parameters in high fat fed Wistar rats

Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Induces Astrocyte Proliferation through the Activation of Transforming-Growth Factor-α/Epidermal Growth Factor Receptor Signaling Pathway

TWEAK prevents TNF-α-induced insulin resistance through PP2A activation in human adipocytes

Contact Info

Product

Resources

About