α-ketoglutarate ameliorated arsenic-induced hepatic lipid deposition in offspring via PI3K/AKT signaling pathway
10.19405/j.cnki.issn1000–1492.2026.02.006
- VernacularTitle:α-酮戊二酸经PI3K/AKT改善砷诱导的子代肝脂质沉积
- Author:
Shuangrui BAO
1
;
Hongyan WU
1
;
Ying SUN
1
;
Tong ZHAN
1
;
Qian YANG
1
;
Xinru LIANG
1
;
Zhiyan WAN
1
;
Wenyi CHEN
2
;
Cheng ZHANG
1
Author Information
1. Department of Toxicology， Anhui Medical University， Hefei 230032
2. Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes， Hefei 230032
- Publication Type:Journal Article
- Keywords:
α-ketoglutarate;
arsenic;
lipid metabolism;
PI3K/AKT;
liver lipid deposition;
gestational exposure;
offspring
- From:
Acta Universitatis Medicinalis Anhui
2026;61(2):225-231
- CountryChina
- Language:Chinese
-
Abstract:
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 （PTuKey<0.05）； the level of hepatic TGs was elevated in arsenic group （PTuKey<0.05）； oil-red O staining showed a significant increase in lipid droplets in arsenic group （PTuKey<0.01）； the expression of lipid synthesis-related genes were significantly upregulated （PTuKey<0.05）； the expression of β-oxidation-related genes and lipid degradation-related genes were downregulated （PTuKey<0.05）； the expression of PI3K， AKT decreased（PTuKey<0.05）. Compared with the arsenic group， the body weight and crown-rump length of fetus increased in the arsenic+α-KG group （PTuKey<0.05）； the level of hepatic TGs decreased in the arsenic+α-KG group （PTuKey<0.05）； oil red O staining showed lipid droplets significantly decreased （PTuKey<0.01）； the expression of lipid synthesis-related genes were downregulated （PTuKey<0.05）， the expression of β-oxidation-related genes and lipid degradation-related genes were upregulated （PTuKey<0.05）； the expression levels of PI3K and AKT increased （PTuKey<0.05）. Conclusionα-KG alleviated hepatic lipid deposition in offspring exposed to arsenic during pregnancy through activating PI3K/AKT signaling pathway.
