Probiotics Intake During Pregnancy Alleviates Fetal NAFLD By Regulating Fatty Acid Oxidation In The Offspring Of Mice

Objective:Nowadays,the incidence of non-alcoholic fatty liver disease(non-alcoholic fatty liver disease,NAFLD)is increasing,and there is a trend of younger generation.The study aims to explore the influence of probiotics on the offspring’s fetal NAFLD by giving probiotics during pregnancy,it provides a new idea for the dietary guidance of the pregnant population and prevents fetal NAFLD from the perspective of nutrition in early life.Methods:Fifty female KM mice weighing 20~25g were randomly divided into a control group(n=10)and a high-fat group(n=40).They were fed with normal diet or high-fat diet for 4 weeks respectively.Afterwards,the female and male mice could be caged together.After successful pregnancy,the pregnant mice in the high-fat group were randomly divided into a high-fat group(HG),a high-fat + low-dose probiotics group(HG-L),and a high-fat + high-dose probiotics group(HG-H).The pregnancy mice in control group(CG)didn’t be divided and fed with normal diet.Before getting the material,the offspring were breast-fed for 21 days and then fed with normal diet for two weeks.By observing liver pathological sections and determining triglyceride(TG),glutathione(GSH),superoxide dismutase(SOD)and malondialdehyde(MDA),analyzed and observed the liver fat accumulation and oxidative damage of offspring.Through measuring the m RNA and protein expression of fatty acid oxidation related genes such as peroxisome proliferator-activated receptor α(PPARα),carnitine palmitoyl transferase-1α(CPT1ɑ),and peroxisome proliferator-activated receptor-γcoactivator-1α,(PGC1α),explored the effect of probiotics intervention during pregnancy on fatty acid oxidation signaling pathways in the liver of offspring.Results:The liver histopathological analysis showed that the high-fat diet during pregnancy and lactation caused the liver lipid accumulation in offspring,leading to the occurrence of fetal NAFLD.Probiotic intervention during pregnancy could reduce the liver fat accumulation in the offspring,and the liver TG level of the offspring in the HG-H group was lower In the HG group(HG-H vs.HG,75.918 ± 4.499 nmol/mg vs.111.726 ± 8.305 nmol/mg,P=0.002).In the offspring,compared with HG,the liver GSH level of HG-H was increased(HG-H vs.HG,3.886 ± 0.508 nmol/mg vs.1.794 ± 0.221 nmol/mg,P=0.045),and the MDA level decreased(HG-H vs.HG,45.123 ± 5.617 nmol/g vs.62.670 ± 3.711 nmol/g,P=0.013).In the offspring,compared with CG group,high-fat diet for female mice could reduce the expression of PGC1α m RNA(HG vs.CG,0.394 ± 0.060 vs.1.046 ± 0.145,P=0.023)and protein(HG vs.CG,0.318 ± 0.030 vs.0.999 ± 0.045,P=0.002)in the offspring.Compared with HG group,while probiotic intervention during pregnancy could up-regulate the m RNA expression of PPARα(HG-H vs HG,2.660 ± 0.330 vs.0.809 ± 0.151,P<0.001),CPT1α(HG-H vs.HG,1.715 ± 0.138 vs.0.952 ± 0.070,P<0.001),and PGC1α(HG-H vs HG,1.715 ± 0.138 vs.1.046 ± 0.145,P<0.001)in the liver of the offspring.Conclusion:High-fat diets in female mice could cause fetal NAFLD in offspring,and probiotics intake during pregnancy could increase the expression of fatty acid oxidation genes in offspring’s liver,reduce fat accumulation,increase liver antioxidant capacity and reduce oxidative damage.