Diacylglycerol O-acyltransferase 1 inhibitor increases plasma alanine aminotransferase and aspartate aminotransferase activities via a shedding of the intestinal villi and an increase in intestinal permeability in rats.
Toxicol Lett
; 400: 16-23, 2024 Oct.
Article
em En
| MEDLINE
| ID: mdl-39096942
ABSTRACT
Diacylglycerol O-acyltransferase 1 (DGAT1) is a key enzyme for fat absorption step in the enterocytes. We previously reported that DGAT1 inhibition increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in corn oil-loaded rats via protein kinase C (PKC) activation. In the present study, we investigated the mechanism with respect to the morphology and permeability of the small intestine, focusing on PKC function, and found that shortening of the intestinal villi and a decrease in the number of tdT-mediated dUTP-biotin nick-end labeling-positive cells in the tips of the villi were observed in the jejunum of DGAT1 inhibitor-treated rats loaded with corn oil. These results suggested that the tips of the villi were shed into the intestinal lumen. Next, fluorescein isothiocyanate-dextran, 110â¯kDa (FD-110) was administered intraduodenally to DGAT1 inhibitor-treated rats loaded with corn oil and we found that plasma FD-110 concentrations increased, indicating that the intestinal permeability to molecules with a molecular weight of approximately 110,000 (e.g., ALT and AST) increased. Taken together, the present results suggested that DGAT1 inhibitor-treatment in combination with corn oil causes ALT and AST to leak from the enterocytes into the blood by shedding the tips of the intestinal villi and increasing intestinal permeability.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Permeabilidade
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Aspartato Aminotransferases
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Óleo de Milho
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Alanina Transaminase
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Diacilglicerol O-Aciltransferase
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Mucosa Intestinal
Limite:
Animals
Idioma:
En
Revista:
Toxicol Lett
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Toxicol. lett
/
Toxicology letters
Ano de publicação:
2024
Tipo de documento:
Article