scholarly journals Toll-Like Receptor-4 Disruption Suppresses Adipose Tissue Remodeling and Increases Survival During Cancer Cachexia Syndrome

2018 ◽  
Author(s):  
Felipe Henriques ◽  
Magno A. Lopes ◽  
Felipe O. Franco ◽  
Pamela Knobl ◽  
Kaltinaitis B. Santos ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cancer Cachexia ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Mass Growth ◽  
Tumor Mass ◽  
Genetic Ablation ◽  
Pharmacological Inhibition ◽  
Tumor Bearing ◽  
Adipose Tissue Remodeling

ABSTRACTCancer-induced cachexia, characterized by systemic inflammation, body weight loss, adipose tissue (AT) remodeling and muscle wasting, is a malignant metabolic syndrome with undefined etiology. Here, we show that Toll-like receptor 4 (TLR4) mediates AT remodeling, in particular, AT browning and inflammatory response in mice bearing Lewis lung carcinoma (LLC). LLC tumor-bearing (TB) TLR4−/− mice were spared from AT remodeling due to a reduced macrophage infiltration and adipocyte atrophy. TLR4−/− mice were also resistant to cold-induced browning of subcutaneous AT (scAT). Importantly, pharmacological inhibition of TLR4 reproduced the main protective effect against AT remodeling found in TLR4−/− TB mice. Moreover, the treatment was effective in prolonging the survival and attenuating tumor mass growth when compared to non-treated-TB animals. Further, tumor-induced elevation of circulating pro-inflammatory cytokines was similarly abolished in both genetic ablation and pharmacological inhibition of TLR4. These data suggest that TLR4 is a critical mediator and a promising therapeutic target for cancer-induced AT remodeling.HIGHLIGHTSGenetic ablation and pharmacological inhibition of TLR4 attenuate adipose tissue remodeling during cancer-associated cachexia;TLR4 suppression play an essential role in the browning phenotype induced by cachexia;Administration of TLR4 drug inhibitor increase survival and reduces tumor mass growth in tumor bearing mice;TLR4 pathway is a promising target for cancer-cachexia therapeutic intervention.

scholarly journals Toll-Like Receptor-4 Disruption Suppresses Adipose Tissue Remodeling and Increases Survival in Cancer Cachexia Syndrome

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Felipe Henriques ◽  
Magno A. Lopes ◽  
Felipe O. Franco ◽  
Pamela Knobl ◽  
Kaltinaitis B. Santos ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cancer Cachexia ◽  
Tissue Remodeling ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Adipose Tissue Remodeling ◽  
Cachexia Syndrome

scholarly journals Potential Role of Toll‐like Receptor 4 in Obesity‐Induced Adipose Tissue Remodeling

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Venkata Jitendra Kumar Adapala ◽  
Sunday Adetayo Adedokun ◽  
Olayiwola Adeola ◽  
Meliza G Ward ◽  
Kolapo Matthew Ajuwon
Keyword(s):  
Adipose Tissue ◽  
Potential Role ◽  
Tissue Remodeling ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Adipose Tissue Remodeling

Contrasting effects of the Toll-like receptor 4 in determining ovarian follicle endowment and fertility in female adult mice

Zygote ◽  
2021 ◽  
pp. 1-7
Author(s):  
Júlio Panzera Gonçalves ◽  
Breno Augusto Magalhães ◽  
Paulo Henrique Almeida Campos-Junior
Keyword(s):  
Ovarian Follicle ◽  
Cumulus Cells ◽  
Toll Like Receptor ◽  
Female Reproduction ◽  
Toll Like Receptor 4 ◽  
Genetic Ablation ◽  
Adult Mice ◽  
Cumulus Oocyte Complex ◽  
Estrous Cyclicity

Abstract Toll-like receptor 4 (TLR4) is best known for its role in bacteria-produced lipopolysaccharide recognition. Regarding female reproduction, TLR4 is expressed by murine cumulus cells and participates in ovulation and in cumulus–oocyte complex (COC) expansion, maternal–fetal interaction and preterm labour. Despite these facts, the role of TLR4 in ovarian physiology is not fully understood. Therefore, the aim of the present study was to investigate the effects of TLR4 genetic ablation on mice folliculogenesis and female fertility, through analysis of reproductive crosses, ovarian responsiveness and follicular quantification in TLR4−/− (n = 94) and C57BL/6 mice [wild type (WT), n = 102]. TLR4-deficient pairs showed a reduced number of pups per litter (P = 0.037) compared with WT. TLR4−/− mice presented more primordial, primary, secondary and antral follicles (P < 0.001), however there was no difference in estrous cyclicity (P > 0.05). A lower (P = 0.006) number of COC was recovered from TLR4−/− mice oviducts after superovulation, and in heterozygous pairs, TLR4−/− females also showed a reduction in the pregnancy rate and in the number of fetuses per uterus (P = 0.007) when compared with WT. Altogether, these data suggest that TLR4 plays a role in the regulation of murine folliculogenesis and in determining ovarian endowment. TLR4 deficiency may affect ovulation and pregnancy rates, potentially decreasing fertility, therefore the potential side effects of its blockade have to be carefully investigated.

scholarly journals Toll-like receptor 4 (TLR4) deficient mice are protected from adipose tissue inflammation in aging

Aging ◽  
2017 ◽  
Vol 9 (9) ◽  
pp. 1971-1982 ◽  
Author(s):  
Amiya K. Ghosh ◽  
Martin O’Brien ◽  
Theresa Mau ◽  
Raymond Yung
Keyword(s):  
Adipose Tissue ◽  
Adipose Tissue Inflammation ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Tissue Inflammation ◽  
Deficient Mice

scholarly journals The Effect of Altered Toll-like Receptor 4 Signaling on Cancer Cachexia

2007 ◽  
Vol 133 (12) ◽  
pp. 1263 ◽  
Author(s):  
Trinitia Y. Cannon ◽  
Denis Guttridge ◽  
Jason Dahlman ◽  
Jonathan R. George ◽  
Victor Lai ◽  
...  
Keyword(s):  
Cancer Cachexia ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4

scholarly journals Effects of Adipose-Derived Biogenic Nanoparticle-Associated microRNA-451a on Toll-like Receptor 4-Induced Cytokines

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 16
Author(s):  
Xinghua Wang ◽  
Anthony Pham ◽  
Lu Kang ◽  
Sierra A. Walker ◽  
Irina Davidovich ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Signaling Pathways ◽  
Extracellular Vesicles ◽  
Inflammatory Cytokines ◽  
Stromal Cells ◽  
Toll Like Receptor ◽  
Immunomodulatory Effects ◽  
Toll Like Receptor 4 ◽  
Biogenic Nanoparticles ◽  
Pro Inflammatory Cytokines

Extracellular vesicles (EVs) are cell-released nanoparticles that transfer biomolecular content between cells. Among EV-associated biomolecules, microRNAs (miRNAs/miRs) represent one of the most important modulators of signaling pathways in recipient cells. Previous studies have shown that EVs from adipose-derived mesenchymal stromal cells (MSCs) and adipose tissue modulate inflammatory pathways in macrophages. In this study, the effects of miRNAs that are abundant in adipose tissue EVs and other biogenic nanoparticles (BiNPs) were assessed in terms of altering Toll-like receptor 4 (TLR4)-induced cytokines. TLR-4 signaling in macrophages is often triggered by pathogen or damage-induced inflammation and is associated with several diseases. This study demonstrates that miR-451a, which is abundant in adipose tissue BiNPs, suppresses pro-inflammatory cytokines and increases anti-inflammatory cytokines associated with the TLR4 pathway. Therefore, miR-451a may be partially responsible for immunomodulatory effects of adipose tissue-derived BiNPs.

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