The effects of high-fat diet on liver damage and pyroptosis in autoimmune hepatitis / 中华传染病杂志

ABSTRACT

Objective To investigate the effect of high-fat diet(HFD)on liver damage caused by autoimmune hepatitis(AIH)in mice.Methods Fifty C57BL/6 male mice were divided randomly into four groupsstandard chow(SC)group,HFD group,AIH + SC group and AIH+ HFD group.AIH model was built after feeding for one week and all mice were sacrificed after four weeks.Liver and spleen tissues and serum were collected. Liver histopathology was detected by HE staining. Serum alanine aminotransperase(ALT)and aspartate aminotransferase(AST)levels were measured.Western blot analysis and real-time polymerase chain reaction(PCR)analysis were used to test the expressions of NLR pyrin domain containing 3(NLRP3)and cysteinyl aspartate specific proteinase 1(Caspase-1).The concentrations of interleukin(IL)-6,IL-1β and tumor necrosis factor(TNF)-α were analyzed using enzyme linked immunosorbent assay technology.The amount of Th17 cells in spleen was analyzed by FACS.Means among groups were analyzed with one-way ANOVA.SNK-q analysis was used for groups with homogeneity of variance, while nonparametric test was used for groups with variance nonhomogeneity.Results Histologically,the H&E staining of liver tissue from HFD group showed adipose degeneration,and there was inflammation around vessel in AIH+SC group.Moreover,in AIH+HFD group,the inflammation was more serious with mildly adipose degeneration.Compared with SC group,serum levels of ALT and AST increased in HFD group and AIH +SC group,and greatest increase was observed in AIH+ HFD group.The differences were statistically significant(F=57.12 and 37.58, both P<0.05).The proportions of Th17 cells in SC group,HFD group,AIH+ SC group and AIH+HFD group were(2.98 ± 0.90)%,(6.89 ± 0.99)%,(6.47 ± 1.08)% and(9.96 ± 0.83)%, respectively.The differences among all groups were statistically significant(F=54.05,P<0.05).The concentrations of IL-1β,IL-6 and TNF-α in each group were as followsSCIL-1β[(7.62 ± 2.81)ng/L],IL-6 [(106.54 ± 53.08)ng/L],T NF-α[(107.26 ± 36.20)ng/L];HFDIL-1β[(25.06 ± 7.09)ng/L],IL-6 [(220.11 ± 47.41)ng/L],TNF-α[(273.77 ± 33.62)ng/L];AIH+SCIL-1β[(17.49 ± 5.68)ng/L],IL-6 [(260.73 ± 50.29)ng/L],TNF-α[(250.49 ± 81.63)ng/L];AIH+ HFDIL-1β[(52.04 ± 10.22)ng/L], IL-6[(785.93 ± 70.91)ng/L],TNF-α[(913.97 ± 64.57)ng/L].The differences were statistically significant(F=44.66,242.15 and 233.49,respectively,all P<0.05).The expressions of NLRP3 and Caspase-1 were significantly increased in AIH+ HFD group than the other three groups(all P<0.05). Conclusions High-fat diet potentiates liver damage induced by autoimmune hepatitis,which might relate to the secretion of pro-inflammatory cytokines,the activation of Th17 cells and the NLRP3 inflammasome as well as pyroptosis.