Glutamine in suppression of lipopolysaccharide-induced piglet intestinal inflammation: The crosstalk between AMPK activation and mitochondrial function.

The study was conducted to investigate the regulatory mechanism of glutamine (Gln) on intestinal inflammation in an lipopolysaccharide ( LPS)-induced in vivo and in vitro models. Piglets ( = 8) weaned at 21 d of age were fed a basal diet (control and LPS groups) or 1% Gln diet (Gln + LPS group) ad libitum for 4 weeks. On d 22, 24, 26 and 28, piglets in the LPS and Gln + LPS groups were intraperitoneally injected with LPS. Intestinal porcine epithelial cells (IPEC-J2) ( = 6) induced by LPS were used to assess related mechanisms and compound C was used to inhibit adenosine 5'-monophosphate-activated protein kinase (AMPK) activity. Our current results showed that compared with the LPS treatment, the Gln + LPS treatment had better growth performance and greater villus height ( < 0.05), and the Gln + LPS treatment reduced the rate of diarrhea by 6.4% ( < 0.05); the Gln + LPS treatment decreased serum tumor necrosis factor (TNF-ɑ), interleukin-6 (IL-6), K, cortisol and insulin levels, whereas increased ( < 0.05) serum immunoglobulin M and epidermal growth factor levels; the Gln + LPS treatment increased ( < 0.05) the expression of aquaporins and AMPK pathway-associated targets in the jejunum and ileum of piglets, whereas decreased the expression of ion transporters ( < 0.05). The in vitro results showed that 4 mmol/L Gln administration could inhibit ( < 0.05) cell apoptosis and interleukin-1β (IL-1β), IL-6 and TNF-ɑ secretion in LPS-induced IPEC-J2 cells, promote ( < 0.05) mitochondrial respiratory metabolism and increase ( < 0.05) the number of mitochondria and mitochondrial membrane potential. The activity of AMPK was elevated by 70% to 300% in Gln-treated IPEC-J2 cells under LPS challenge or normal conditions. Our results indicate that pre-administration of Gln to piglets suppresses intestinal inflammation by modulating the crosstalk between AMPK activation and mitochondrial function.