Deletion of TLR4 Attenuates Adipose Tissue Inflammation in Cancer Cachexia

Abstract

Several studies have shown that syndrome of cachexia associated with cancer induces a drastic decrease in body weight and adipose tissue. Stimulation of TLR4 activates proinflammatory pathways and induces cytokine expression in a variety of cell types. Inflammatory pathways are activated in tissues of cachectic animals and play an important role in cancer‐cachexia syndrome. Loss of adipose tissue mass and inflammation occurred early considering the appearance of classical cachexia markers. In this study we evaluated cachexia development in TLR4 ‐/‐ mice. Male C57BL/6 mice, with 300µl (3,5 ×105) of LLC tumor cells or vehicle‐saline. Adipose tissue (SCAT, MEAT, RPAT) were collected on 27th day after cells injection. The SVF of AT was isolated and measured the infiltrated immune cells (macrophage and T lymphocytes) by Flow cytometry. SCAT (TWT 37,2% and TM 70,7%), MEAT (TWT 27,1% and TM 28,8%), RPAT (TWT 27,4% and TM 76,9%) showed an decrease of total mass on 27th. In flow cytometry using GR and MAC1 showed an accentuated decrease in MEAT of the TLR4 ‐/‐ mice when compared whit the Wild type mice, in both groups (CWT 77,5% and TWT 66,3%). We observed an accentuated body weight loss in both groups, WT and TLR4 ‐/‐. Therefore when we look at the MEAT, compared with the other depots of TLR4 ‐/‐ mice, presents an attenuated in tissue mass, besides occurring decreased of the most important inflammatory cells in to adipose tissue, characteristic during of the cachectic syndrome. Suggesting that deletion of TLR4 protein may play a role in adipose tissue inflammation.