Glutamine Administration Attenuates Kidney Inflammation in Obese Mice Complicated with Polymicrobial Sepsis

Figure 7

The proposed mechanisms of glutamine (GLN) regulation on attenuating sepsis-induced acute kidney injury (AKI). Obesity exaggerates the severity of sepsis, and AKI is a common complication. Underlying sepsis, immune cells release inflammatory cytokines and chemokines that result in systemic inflammation. In the kidney, upregulation of HMGB-1 activates the NF-κB pathway and subsequent downstream inflammatory mediator production. Activated macrophage and neutrophil infiltration into kidney tissue may worsen the integrity of tight junction and increase the production of lipid peroxides. The inflammatory microenvironment within renal cells ultimately leads to AKI. GLN administration increases the plasma levels of GLN, blocks the inflammatory pathways, and reduces lipid peroxide production, thus ameliorating the occurrence of AKI. Red line means the effects of obesity complicated with sepsis. Blue line means the effects of GLN administration on obesity complicated with sepsis. CD68: cluster of differentiation 68; CLP: cecal ligation and puncture; EMR-1: epidermal growth factor-like module-containing mucin-like hormone receptor-like-1; HMGB-1: high-mobility group box protein-1; KC: keratinocyte-derived chemokine; IL: interleukin; MCP-1: monocyte chemoattractant protein-1; MDA: malondialdehyde; MPO: myeloperoxidase; MyD88: myeloid differentiation factor 88; NF-κB: nuclear factor-κB; PLF: peritoneal lavage fluid; TLR4: toll-like receptor-4; TNF-α: tumor necrosis factor-α; ZO-1, zonula occluden-1.