Gestational α-ketoglutarate supplementation ameliorates arsenic-induced hepatic lipid deposition via epigenetic reprogramming of ß-oxidation process in female offspring.
Environ Int
; 185: 108488, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38359550
ABSTRACT
Inorganic trivalent arsenic (iAsâ
¢) at environmentally relevant levels has been found to cause developmental toxicity. Maternal exposure to iAsâ
¢ leads to enduring hepatic lipid deposition in later adult life. However, the exact mechanism in iAsâ
¢ induced hepatic developmental hazards is still unclear. In this study, we initially found that gestational exposure to iAsâ
¢ at an environmentally relevant concentration disturbs lipid metabolism and reduces levels of alpha-ketoglutaric acid (α-KG), an important mitochondrial metabolite during the citric acid cycle, in fetal livers. Further, gestational supplementation of α-KG alleviated hepatic lipid deposition caused by early-life exposure to iAsâ
¢. This beneficial effect was particularly pronounced in female offspring. α-KG partially restored the ß-oxidation process in hepatic tissues by hydroxymethylation modifications of carnitine palmitoyltransferase 1a (Cpt1a) gene during fetal development. Insufficient ß-oxidation capacities probably play a crucial role in hepatic lipid deposition in adulthood following in utero arsenite exposure, which can be efficiently counterbalanced by replenishing α-KG. These results suggest that gestational administration of α-KG can ameliorate hepatic lipid deposition caused by iAsâ
¢ in female adult offspring partially through epigenetic reprogramming of the ß-oxidation pathway. Furthermore, α-KG shows potential as an interventive target to mitigate the harmful effects of arsenic-induced hepatic developmental toxicity.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Arsênio
/
Arsenicais
/
Intoxicação por Arsênico
Idioma:
En
Revista:
Environ Int
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China