Altered Expression of Retinol Metabolism-Related Genes in an ANIT-Induced Cholestasis Rat Model

Abstract

Cholestasis is defined as a reduction of bile secretion caused by a dysfunction of bile formation. Insufficient bile secretion into the intestine undermines the formation of micelles, which may result in the reduced absorption of lipids and fat-soluble vitamins. Here, we investigated the retinol homeostasis and the alterations of retinol metabolism-related genes, including β-carotene 15,15′ monooxygenase (BCMO), lecithin:retinol acyltransferase (LRAT), aldehyde dehydrogenase (ALDH), cytochrome P450 26A1 (CYP26A1), and retinoic acid receptors (RAR) β, in a α-naphthyl isothiocyanate (ANIT)-induced cholestasis rat model. Moreover, we examined the expression of the farnesoid X receptor (FXR) target genes. Our results showed that plasma retinol levels were decreased in ANIT rats compared to control rats. On the contrary, hepatic retinol levels were not different between the two groups. The expression of FXR target genes in the liver and intestine of cholestasis model rats was repressed. The BCMO expression was decreased in the liver and increased in the intestine of ANIT rats compared to control rats. Finally, the hepatic expression of LRAT, RARβ, and ALDH1A1 in cholestatic rats was decreased compared to the control rats, while the CYP26A1 expression of the liver was not altered. The increased expression of intestinal BCMO in cholestasis model rats might compensate for decreased circulatory retinol levels. The BCMO expression might be regulated in a tissue-specific manner to maintain the homeostasis of retinol.

The zhuyu pill relieves rat cholestasis by regulating the mRNA expression of lipid and bile metabolism associated genes

“…Steroid hormone biosynthesis also promotes cholesterol conversion and bile acid synthesis, increasing cholesterol excretion from the liver ( Sun et al, 2021 ). The current study found that retinol metabolism was significantly inhibited in the livers of rats in the cholestasis model, which supports previous studies ( Cai et al, 2014 ; Takitani et al, 2018 ; Yuan et al, 2018 ). Retinoic acid may improve lipid deposition.…”

The in vitro digestion fates of diacylglycerol under different intestinal conditions: a potential lipid source for lipid indigestion patients

“…Owing to their distinct chemical structure, bile salts possess surfactant/detergent-like properties and are important contributors to micellar solubilization of dietary lipids (mainly TAGs). The impairments of bile formation and secretion cause the reduction of bile salts secretion or obstruction of bile fl ow (which is called "cholestasis") [4] . Chronic cholestasis causes malabsorption of vital micronutrients [5] .…”