A new link between innate immunity and hepatic metabolism:attractive unknown place to visit
The potential role of gut microbial products is one of the most highlighted issues in nonalcoholic steatohepatitis (NASH) and type 2 diabetes. Gut dysbiosis and increased intestinal permeability are considered to enhance the translocation of microbial products such as endotoxin (lipopolysaccharide: LPS). This in turn activates toll-like receptors (TLRs) inducing inflammatory changes in target tissues and organs. TLR signaling pathways thus build a bridge between the gut microbiome and host organs. Each TLR detects a specific pathogen-associated molecular pattern (PAMP). TLR4 detects endotoxin from Gram-negative bacteria, while TLR2 detects bacterial lipoprotein and peptidoglycan and TLR5 detects bacterial flagellin. Intracellular TLR3 and TLR9 are activated by microbe-derived nucleic acids (1). In addition to endotoxin, endogenous ligands such as free fatty acids are known to stimulate TLR4, which may predispose to systemic low-grade inflammation and insulin resistance in patients with NASH and type 2 diabetes. Hepatocyte-specific Tlr4 deletion was reported to ameliorate hepatic steatosis, inflammation and insulin resistance in mice fed a high-fat diet (HFD) (2).
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2019-07-18（万方平台首次上网日期，不代表论文的发表时间）
共4页
264-267
