ObjectiveTo investigate the protective effect of α-ketoglutarate （α-KG） on hepatic lipid deposition in offspring caused by arsenic exposure during pregnancy. Methods8-week-old institute of cancer research （ICR） mice were mated in a ratio of 2∶1 between females and males， and the detection of vaginal plugs confirmed pregnant. A total of 32 pregnant mice were randomly divided into four groups： control group， arsenic group， α-KG group， arsenic+α-KG group. On gestational day 0-16 （GD0-GD16）， the arsenic and arsenic+α-KG groups were exposed to sodium arsenite （NaAsO₂ ，15 mg/L） in drinking water everyday， and the α-KG and arsenic+α-KG groups were gavaged with α-KG （2 g/kg） everyday. On GD16， pregnant mice were euthanized to collect fetal liver， and fetal body weight and crown-rump length were measured. Gene expression differences between the control group and the arsenic group were analyzed by transcriptome. The total triglycerides （TGs） and subtypes in fetal liver were detected by liquid chromatography tandem mass spectrometry （LC-MS/MS）. Oil red O staining was used to observe the histopathological changes in the liver. Quantitative polymerase chain reaction （qPCR） was used to detect the expression level of genes related to lipid synthesis， transport， and degradation， and phosphatidylinositol 3' -kinase/ protein kinase B （PI3K/AKT） in the liver of fetus. ResultsTranscriptomics analysis showed that 2 144 genes were downregulated and 1 675 genes were upregulated in the arsenic exposed fetal liver； body weight and crown-rump length were reduced （P_TuKey<0.05）； the level of hepatic TGs was elevated in arsenic group （P_TuKey<0.05）； oil-red O staining showed a significant increase in lipid droplets in arsenic group （P_TuKey<0.01）； the expression of lipid synthesis-related genes were significantly upregulated （P_TuKey<0.05）； the expression of β-oxidation-related genes and lipid degradation-related genes were downregulated （P_TuKey<0.05）； the expression of PI3K， AKT decreased（P_TuKey<0.05）. Compared with the arsenic group， the body weight and crown-rump length of fetus increased in the arsenic+α-KG group （P_TuKey<0.05）； the level of hepatic TGs decreased in the arsenic+α-KG group （P_TuKey<0.05）； oil red O staining showed lipid droplets significantly decreased （P_TuKey<0.01）； the expression of lipid synthesis-related genes were downregulated （P_TuKey<0.05）， the expression of β-oxidation-related genes and lipid degradation-related genes were upregulated （P_TuKey<0.05）； the expression levels of PI3K and AKT increased （P_TuKey<0.05）. Conclusionα-KG alleviated hepatic lipid deposition in offspring exposed to arsenic during pregnancy through activating PI3K/AKT signaling pathway.

ObjectiveTo explore the ameliorative effect of the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid （4-PBA） on bile acid metabolism disorders induced by bacterial lipopolysaccharide （LPS） in late-pregnant mice， and to clarify the regulatory mechanism of endoplasmic reticulum stress （ERS） in intrahepatic cholestasis of pregnancy （ICP）. MethodsTwenty-four pregnant mice were divided into control group， LPS group， 4-PBA group， and LPS+4-PBA group. On the 16th day of pregnancy， the LPS group received intraperitoneal injection of LPS （200 μg/kg） and the 4-PBA group received injection of 4-PBA （150 mg/kg）. In the LPS+4-PBA group， 4-PBA was intraperitoneally injected first， followed by LPS administration 1 h later. Serum total bile acid （TBA）， liver injury markers， bile acid profiles， and the expression of key genes and proteins were detected 6 h after LPS treatment. ResultsLPS exposure increased serum TBA levels in pregnant mice（P<0.05）， activated ERS markers and inflammatory factors， and downregulated bile acid transporters and the expression of the rate limiting enzyme CYP7A1（all P<0.05）. 4-PBA intervention effectively inhibited ERS， reduced TBA levels（P<0.05）， and upregulated Ntcp， Bsep， Mdr3， and Mrp3 gene expression（all P<0.05）. ConclusionERS plays an important role in LPS interference with the homeostasis of bile acid metabolism during pregnancy. Inhibiting ERS can improve bile stasis by regulating bile acid transporters， providing a theoretical basis for targeted therapy of ICP.