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

摘要

The study was conducted to investigate the regulatory mechanism of glutamine(Gln)on intestinal inflammation in an Escherichia coli lipopolysaccharide(E.coli LPS)-induced in vivo and in vitro models.Piglets(n=8)weaned at 21 d of age were fed a basal diet(control and LPS groups)or 1%Gln diet(Gln t LPS group)ad libitum for 4 weeks.On d 22,24,26 and 28,piglets in the LPS and Gln t LPS groups were intraperitoneally injected with E.coli LPS.Intestinal porcine epithelial cells(IPEC-J2)(n=6)induced by LPS were used to assess related mechanisms and compound C was used to inhibit adenosine 50-monophosphate-activated protein kinase(AMPK)activity.Our current results showed that compared with the LPS treatment,the Gln t LPS treatment had better growth performance and greater villus height(P<0.05),and the Gln t LPS treatment reduced the rate of diarrhea by 6.4%(P<0.05);the Gln t LPS treatment decreased serum tumor necrosis factor(TNF-ɑ),interleukin-6(IL-6),Kt,cortisol and insulin levels,whereas increased(P<0.05)serum immunoglobulin M and epidermal growth factor levels;the Gln t LPS treatment increased(P<0.05)the expression of aquaporins and AMPK pathwayassociated targets in the jejunum and ileum of piglets,whereas decreased the expression of ion transporters(P<0.05).The in vitro results showed that 4 mmol/L Gln administration could inhibit(P<0.05)cell apoptosis and interleukin-1b(IL-1b),IL-6 and TNF-ɑsecretion in LPS-induced IPEC-J2 cells,promote(P<0.05)mitochondrial respiratory metabolism and increase(P<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.