scholarly journals Distribution and regulation of plasminogen activator inhibitor-1 in murine adipose tissue in vivo. Induction by tumor necrosis factor-alpha and lipopolysaccharide.

1996 ◽  
Vol 97 (1) ◽  
pp. 37-46 ◽  
Author(s):  
F Samad ◽  
K Yamamoto ◽  
D J Loskutoff
Keyword(s):  
Adipose Tissue ◽  
Tumor Necrosis ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Activator Inhibitor ◽  
Necrosis Factor ◽  
In Vivo Induction

scholarly journals Increased adipose tissue secretion of interleukin-6, but not of leptin, plasminogen activator inhibitor-1 or tumour necrosis factor alpha, in Graves' hyperthyroidism

2002 ◽  
pp. 607-611 ◽  
Author(s):  
H Wahrenberg ◽  
A Wennlund ◽  
J Hoffstedt
Keyword(s):  
Adipose Tissue ◽  
Plasminogen Activator Inhibitor ◽  
Tumour Necrosis Factor Alpha ◽  
Tnf Alpha ◽  
Plasminogen Activator Inhibitor 1 ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Activator Inhibitor ◽  
Necrosis Factor ◽  
Pai 1

OBJECTIVE: This study was designed to investigate adipose tissue secretion of interleukin-6 (IL-6), leptin, tumour necrosis factor alpha (TNF-alpha) and plasminogen activator inhibitor-1 (PAI-1) in Graves' hyperthyroidism. DESIGN: We studied 10 patients before and during (after 8 weeks) anti-thyroid treatment for Graves' hyperthyroidism and 16 healthy, euthyroid control subjects. METHODS: Plasma levels of thyroid hormones and serum/plasma levels of IL-6, leptin, TNF-alpha and PAI-1 were analysed. Subcutaneous fat biopsies were taken for subsequent measurement of IL-6, leptin, TNF-alpha and PAI-1 protein secretion. RESULTS: In patients with Graves' disease, the anti-thyroid treatment resulted in significant reductions of plasma thyroxine and triiodothyronine levels. No differences in serum concentration or adipose tissue secretion of leptin or TNF-alpha were observed either before, as compared with during, anti-thyroid treatment, or in comparison with euthyroid controls. In contrast, plasma PAI-1 activity, but not adipose tissue secretion of PAI-1, was increased both in Graves' disease before as compared with during anti-thyroid treatment (P=0.01) and in thyrotoxic patients compared with euthyroid controls (P=0.0001). Finally, adipose secretion of IL-6 was increased both before (8-fold, P=0.001) and during (6-fold, P<0.0001) treatment as compared with control subjects. Accordingly, serum concentration of IL-6 was also increased by about 50% in thyrotoxic patients as compared with healthy controls (P=0.03). CONCLUSIONS: In Graves' hyperthyroidism regardless of thyroid status, adipose tissue secretion of IL-6, but not of leptin, TNF-alpha or PAI-1, is markedly increased in comparison with euthyroid controls. This suggests that autoimmune thyroidal disorder may regulate adipose tissue release of IL-6.

scholarly journals Nuclear c-Myc plays an important role in the cytotoxicity of tumor necrosis factor alpha in tumor cells.

1994 ◽  
Vol 14 (9) ◽  
pp. 5661-5670 ◽  
Author(s):  
R U Jänicke ◽  
F H Lee ◽  
A G Porter
Keyword(s):  
Tumor Necrosis ◽  
Plasminogen Activator Inhibitor ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Activator Inhibitor ◽  
Necrosis Factor

The phosphoprotein c-Myc has the potential to kill cells by apoptosis. To investigate whether c-Myc is involved in tumor necrosis factor alpha (TNF-alpha)-mediated cell killing, we have examined two HeLa cell lines (D98 and H21) which show dramatic differences in their susceptibilities to TNF-alpha cytotoxicity. Northern (RNA) blot analyses showed that there were no significant differences between these cell lines in basal or TNF-alpha-induced mRNA expression for a variety of proteins, including manganous superoxide dismutase, A20 zinc finger protein, plasminogen activator inhibitor type 2, and hsp70, all of which are known to influence the susceptibility of certain cells to TNF-alpha killing. On the other hand, there was a dramatic increase in c-Myc mRNA expression in TNF-alpha-sensitive D98 cells, but not in TNF-alpha-resistant H21 cells, which was only observed when the cells were treated with cycloheximide. Western blot (immunoblot) analyses revealed that even in the absence of TNF-alpha or cycloheximide, c-Myc was detectable only in nuclear extracts of TNF-alpha-sensitive D98 cells, implying a role for preexisting c-Myc in TNF-alpha killing. In support of this interpretation, a c-myc antisense oligonucleotide specifically inhibited the TNF-alpha killing of D98 cells, provided that the oligonucleotide was added 6 h prior to TNF-alpha treatment. Either dexamethasone treatment or transient expression of c-myc antisense cDNA fragments decreased nuclear c-Myc in D98 cells and rendered the cells more resistant to TNF-alpha cytotoxicity. Nuclear c-Myc was also detectable in a TNF-alpha-sensitive human HT-1080 fibrosarcoma cell line, but it was undetectable in a derivative of HT-1080 (SS-HT-1080) known to be resistant to TNF-alpha killing because of overexpression of plasminogen activator inhibitor type 2. HT-1080 cells transfected with antisense c-myc cDNA had significantly less nuclear c-Myc and were resistant to TNF-alpha cytotoxicity. Together, these data indicate that a nuclear transcription factor, c-Myc, plays an important role in sensitizing two different tumor cell types to TNF-alpha cytotoxicity.

scholarly journals Obesity-Induced Tumor Necrosis Factor Alpha Suppresses In Vivo and In Vitro Retinoic Acid Synthesis and Fatty Acid Oxidation in Adipose Tissue

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 955-955
Author(s):  
Seok-Yeong Yu ◽  
Zhenhua Liu ◽  
Soonkyu Chung ◽  
Young-Cheul Kim
Keyword(s):  
Adipose Tissue ◽  
Tumor Necrosis ◽  
Inflammatory Responses ◽  
Acid Oxidation ◽  
Necrosis Factor Alpha ◽  
Raw264.7 Macrophages ◽  
Factor Alpha ◽  
Necrosis Factor

Abstract Objectives Obese adipose tissue (AT) is characterized by decreased fatty acid oxidation (FAO) and overexpression of tumor necrosis factor alpha (TNFα), a potent proinflammatory mediator of AT dysfunction and metabolic diseases. Several studies have shown that biosynthesis of retinoic acid (RA) from retinol (vitamin A) is suppressed in obese AT. RA has been identified as an agonist for peroxisome proliferator-activated receptor beta/delta (PPARβ/δ), a critical inducer of FAO. The present study aimed to identify a potential mediator of suppressing RA synthesis and thus metabolic dysregulation by (1) evaluating the role of TNFa in tissue RA synthesis and metabolism in vivo and (2) investigating the potential roles of all trans-RA (ATRA) against TNFa-induced AT dysfunction in vitro. We hypothesized that altered retinoid metabolism in obese AT leads to AT dysfunction by reducing PPARβ/δ expression in adipocytes and macrophages. Methods Wild-type (WT) or TNFa knockout (KO) mice were fed a high-fat diet (HFD) or a low-fat diet (LFD) for 16 weeks. Selected serum biochemical parameters as well as expression of genes related to FAO and retinol metabolism were assessed by qPCR and Western Blot analysis. 3T3-L1 adipocytes and RAW264.7 macrophages were also employed to evaluate the effect of TNFa and ATRA on RA synthesis and pro-inflammatory responses. Results We found that RA concentration was significantly attenuated in epididymal AT from HFD-fed TNFa KO group concomitant with the upregulation of genes for RA synthesis (RDH10 & RALDH1) and PPARβ/δ compared to HFD-fed WT group. In 3T3-L1 adipocytes, TNFa treatment significantly inhibited RA synthesis from retinol and downregulated the expression of RDH10 & RALDH1 genes and FAO makers (PPARβ/δ protein and CPT1 mRNA). Furthermore, ATRA treatment significantly increased the expression of PPARβ/δ protein and CPT1 mRNA in TNFα-treated cells. In addition, ATRA significantly suppressed adipocyte-conditioned medium-induced inflammatory responses in RAW264.7 macrophages by increasing PPARβ/δ expression. Conclusions These findings suggest that TNFα overexpressed in obesity mediates AT dysfunction by impairing RA synthesis and ATRA may confer protection against obesity-induced metabolic comorbidities. Funding Sources This project was partially supported by the US Department of Agricultural Experiment Station (MAS00503).

Impact of Physical Activity Intensity Levels on the Cardiometabolic Risk Status of Children: The Genobox Study

2021 ◽  
pp. 1-9
Author(s):  
Francisco J. Llorente-Cantarero ◽  
Francisco J. Aguilar-Gómez ◽  
Gloria Bueno-Lozano ◽  
Augusto Anguita-Ruiz ◽  
Azahara I. Rupérez ◽  
...  
Keyword(s):  
Physical Activity ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cardiometabolic Risk ◽  
Plasminogen Activator Inhibitor ◽  
Necrosis Factor Alpha ◽  
Tissue Plasminogen ◽  
Factor Alpha ◽  
Activator Inhibitor ◽  
Necrosis Factor

Childhood obesity has been related to metabolic syndrome and low-grade chronic inflammation. This study aimed to evaluate the impact of physical activity intensities and practice on inflammation, endothelial damage, and cardiometabolic risk factors in children. There were 513 participants, aged 6–14 years, recruited for the study. Physical activity was measured by accelerometry, and the children were classified into four groups according to quartiles of moderate to vigorous physical activity (MVPA) practice as very low active, low active, moderate active, and high active. Anthropometric measures, blood pressure, and plasma metabolic and proinflammatory parameters were analyzed. Very low active group presented a worse lipid profile and higher insulin, leptin, adiponectin, resistin, matrix metallopeptidase-9, and tissue plasminogen activator inhibitor-1, while lower levels of tumor necrosis factor-alpha, Type 1 macrophages, and interleukin 8 than high-active children. Regression analyses showed that a higher MVPA practice was associated with lower levels of triacylglycerols (β: −0.118; p = .008), resistin (β: −0.151; p = .005), tPAI (β: −0.105; p = .046), and P-selectin (β: −0.160; p = .006), independently of sex, age, and body mass index (BMI). In contrast, a higher BMI was associated with higher levels of insulin (β: 0.370; p < .001), Homeostasis Model Assessment (β: 0.352; p < .001), triacylglycerols (β: 0.209; p < .001), leptin (β: 0.654; p < .001), tumor necrosis factor-alpha (β: 0.182; p < .001), Type 1macrophages (β: 0.181; p < .001), and tissue plasminogen activator inhibitor (β: 0.240; p < .001), independently of sex, age, and MVPA. A better anthropometric, metabolic, and inflammatory profile was detected in the most active children; however, these differences were partly due to BMI. These results suggest that a higher MVPA practice and a lower BMI in children may lead to a better cardiometabolic status.

scholarly journals Nuclear c-Myc plays an important role in the cytotoxicity of tumor necrosis factor alpha in tumor cells

1994 ◽  
Vol 14 (9) ◽  
pp. 5661-5670
Author(s):  
R U Jänicke ◽  
F H Lee ◽  
A G Porter
Keyword(s):  
Tumor Necrosis ◽  
Plasminogen Activator Inhibitor ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Activator Inhibitor ◽  
Necrosis Factor

The phosphoprotein c-Myc has the potential to kill cells by apoptosis. To investigate whether c-Myc is involved in tumor necrosis factor alpha (TNF-alpha)-mediated cell killing, we have examined two HeLa cell lines (D98 and H21) which show dramatic differences in their susceptibilities to TNF-alpha cytotoxicity. Northern (RNA) blot analyses showed that there were no significant differences between these cell lines in basal or TNF-alpha-induced mRNA expression for a variety of proteins, including manganous superoxide dismutase, A20 zinc finger protein, plasminogen activator inhibitor type 2, and hsp70, all of which are known to influence the susceptibility of certain cells to TNF-alpha killing. On the other hand, there was a dramatic increase in c-Myc mRNA expression in TNF-alpha-sensitive D98 cells, but not in TNF-alpha-resistant H21 cells, which was only observed when the cells were treated with cycloheximide. Western blot (immunoblot) analyses revealed that even in the absence of TNF-alpha or cycloheximide, c-Myc was detectable only in nuclear extracts of TNF-alpha-sensitive D98 cells, implying a role for preexisting c-Myc in TNF-alpha killing. In support of this interpretation, a c-myc antisense oligonucleotide specifically inhibited the TNF-alpha killing of D98 cells, provided that the oligonucleotide was added 6 h prior to TNF-alpha treatment. Either dexamethasone treatment or transient expression of c-myc antisense cDNA fragments decreased nuclear c-Myc in D98 cells and rendered the cells more resistant to TNF-alpha cytotoxicity. Nuclear c-Myc was also detectable in a TNF-alpha-sensitive human HT-1080 fibrosarcoma cell line, but it was undetectable in a derivative of HT-1080 (SS-HT-1080) known to be resistant to TNF-alpha killing because of overexpression of plasminogen activator inhibitor type 2. HT-1080 cells transfected with antisense c-myc cDNA had significantly less nuclear c-Myc and were resistant to TNF-alpha cytotoxicity. Together, these data indicate that a nuclear transcription factor, c-Myc, plays an important role in sensitizing two different tumor cell types to TNF-alpha cytotoxicity.

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