Mechanism of immune attack in the progression of obesity-related type 2 diabetes

Figure 1 Immune attack and inflammation in the gut during obesity-related type 2 diabetes. In the context of obesity and type 2 diabetes mellitus, overnutrition leads to the reduced gut microbiota, and even the increase of opportunistic pathogens. At the same time, the occurrence of decreased metabolites levels with anti-inflammatory effects, is accompanied by the activation of inflammation signaling. During obesity, imbalance of pro- and anti-inflammatory immune cells occurs in the gut. The intestinal epithelial cell-produced monocyte chemoattractant protein-1 (MCP1) recruits the circulating monocytes to the gut and they shift to the pro-inflammatory phenotype. High fat diet also induces a pro-inflammatory shift in T cells, accompanied with decreased regulatory T cells. Immunoglobulin A (IgA)-secreting immune cells and IgA secretion are both decreased. High-calorie diet and several recruited immune cells also impair intestinal barrier and increase intestinal epithelial and gut vascular permeability, leading to the leakage of microbiota-derived molecules (such as lipopolysaccharide [LPS]) into blood. High levels of LPS and other bacterial products cause endotoxemia and inflammation in multiple organs that further aggravate the metabolic diseases. GPR: G protein-coupled receptor; SCFAs: Short-chain fatty acids.