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

Figure 3 Immune attack and inflammation in the liver in obesity-related type 2 diabetes. Under metabolic stress, recruited hepatic macrophages, which are derived from circulating monocytes, are recruited by steatosis hepatocytes and Kupffer cells secreting monocyte chemoattractant protein-1 (MCP1). Expanded adipose tissue-derived free fatty acids, leptin, interleukin-1 beta (IL-1β) and bacteria with their products from gut, contribute to the M1 polarization of hepatic macrophages. Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease, which is associated with more severe hepatic insulin resistance and inflammation. The infiltration of neutrophils, B2 cells, interferon gamma (IFN-γ)-producing CD4+ T cells and IFN-α-producing CD8+ T cells occur in NASH liver, promoting insulin resistance under diet-induced metabolic stress. FFAs: Free fatty acids; KCs: Kupffer cells; LPS: Lipopolysaccharide; mEVs: Extracellular vesicles.