Ke Zhang, Xue Li, Xian Wang, Hongyu Zheng, Shusheng Tang, Lin Lu* and Xi Ma* Pages 978 - 984 ( 7 )
Serotonin (5-hydroxytryptamine, 5-HT) has been recognized as a potent pro-inflammatory mediator. Increasing the bioavailability and preventing the formation of 5-HT can reduce the inflammatory response in the body. Moreover, 5-HT is considered as an important central physiologic mediator of intestinal function by regulating intestinal motility, permeability, and other functions. The dysfunction of intestinal serotonergic system causes intestinal barrier damage and further leads to the increase of bacterial endotoxin (LPS) translocation into the liver, which contributes to the development of non-alcoholic fatty liver disease (NAFLD). In addition, increasing the expression of serotonin reuptake transporter (SERT) and decreasing the expression of tryptophan hydroxylase1 (TPH1) can relieve the symptoms of NAFLD. Tryptophan (TRP), as a precursor of 5-HT synthesis, plays an important role in gut homeostasis and energy metabolism. Previous studies have found that TRP supplementation aggravates fatty liver degeneration by producing 5-HT, which activates mTOR signaling pathway in mice fed a high fat and high fructose diet. However, recent researches reveal that TRP supplementation stabilizes the intestinal barrier damage by increasing the expression of occludin and reduces the accumulation of fatty acids in liver. Although the effects of TRP supplementation on NAFLD are not clear and the specific mechanism needs to be further explored. A better understanding of the mechanisms of 5-HT on the liver and gut may open new therapeutic strategies in NAFLD.
Serotonin, non-alcoholic fatty liver disease, intestinal barrier, endotoxin, tryptophan, mTOR.
State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, Animal Science and Technology College, Beijing University of Agriculture, Beijing 102206, Animal Science and Technology College, Beijing University of Agriculture, Beijing 102206, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, Department of Emergency, Affiliated Hospital 1, Kunming Medical University, 295 Xichang Rd, Kunming, Yunnan, Animal Science and Technology College, Beijing University of Agriculture, Beijing 102206, State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193