Acyl-CoA:diacylglycerol acyltransferase 1 inhibition in the small intestine increases plasma transaminase activity via the activation of protein kinase C pathway

Abstract

Acyl-CoAdiacylglycerol acyltransferase 1 (DGAT1) is a key enzyme in the fat absorption step in enterocytes. We previously reported that the pharmacological inhibition of DGAT1 increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in corn oil-loaded rats without any sign of hepatotoxicity. In this study, we investigated this mechanism. We found that this elevation occurred only during the pharmacologically active period of a DGAT1 inhibitor and the magnitude did not depend on the volume of corn oil. In addition, this elevation was not accompanied by increases in ALT or AST mRNA levels in the small intestine and liver. To clarify a lipid component responsible for this elevation, rats were treated with free fatty acids instead of corn oil and no plasma ALT elevation was observed. Next, rats were pretreated with inhibitors of monoacylglycerol acyltransferase 2 and intestinal microsomal triglyceride transfer protein instead of the DGAT1 inhibitor, but no plasma ALT elevation was observed after corn oil loading. Since the results suggested a possible role of diacylglycerol (DAG), which activates protein kinase C (PKC), we measured PKC activity in the small intestine and found that the activity was increased by treatment with the DGAT1 inhibitor and corn oil. Moreover, rats pretreated with a PKC inhibitor in combination with the DGAT1 inhibitor showed suppression of plasma ALT elevation. Taken together, the present results suggest that DAG accumulation induced by pharmacological DGAT1 inhibition and resultant PKC activation in enterocytes are involved in the increase in plasma ALT and AST activity in rats.

Effect of Active Compounds for Quercus Fruit on Some Biochemical Parameters and Tissue Aorta in Induced Atherosclerosis Rats

“…The treatment of animals with cholesterol at a concentration of 500 mg/kg of body weight led to their infection with atherosclerosis with a significant P ≤ 0.05 increase in chol, T.G LDL-C in the blood plasma during the treatment period (15) days (Ram et al,2014;Kang et al, 2019 ) as shown in Table (4 formation of cholesterol and thus reduce the level of excess cholesterol to bile acids and then to the intestinal tract and thus excreted by the seed and activation lipoprotein lipase enzyme (Yokoyama., et al, 2022 ;Wen etal.,2022), Also, results shown in table (4…”