Massive bowel resection upregulates the intestinal mRNA expression levels of cellular retinol-binding protein II and apolipoprotein A-IV and alters the intestinal vitamin A status in rats

Abstract

Abstract. Short bowel (SB) syndrome causes the malabsorption of various nutrients. Among these, vitamin A is important for a number of physiological activities. Vitamin A is absorbed by epithelial cells of the small intestine and is discharged into the lymphatic vessels as a component of chylomicrons and is delivered to the liver. In the present study, we used a rat model of SB syndrome in order to assess its effects on the expression of genes associated with the absorption, transport and metabolism of vitamin A. In the rats with SB, the intestinal mRNA expression levels of cellular retinol-binding protein II (CRBP II, gene symbol Rbp2) and apolipoprotein A-IV (gene symbol Apoa4) were higher than those in the sham-operated rats, as shown by RT-qPCR. Immunohistochemical analysis revealed that absorptive epithelial cells stained positive for both CRBP II and lecithin retinol acyltransferase, which are both required for the effective esterification of vitamin A. In the rats with SB, the retinol content in the ileum and the retinyl ester content in the jejunum were lower than those in the sham-operated rats, as shown by quantitative analysis of retinol and retinyl esters by high performance liquid chromatography. These results suggest that the elevated mRNA expression levels of Rbp2 and Apoa4 in the rats with SB contribute to the effective esterification and transport of vitamin A. IntroductionShort bowel (SB) syndrome occurs as a consequence of malabsorption from an intestinal surface area insufficient to maintain growth and a normal nutritional status (1,2). Intestinal adaptation is a well-known phenomenon that increases the absorptive capacity following surgical resection of the small intestine. The most prominent feature of intestinal adaptation is the proliferation of intestinal cells that increases crypt depth and enlarges the length and width of the villi (3). It is known that micronutrients affect several aspects of intestinal adaptation. Wang et al (4) reported that intestinal adaptation was facilitated by retinoic acid, an active form of vitamin A. The authors demonstrated that the intravenous administration of retinoic acid exerted trophic effects in rats with SB by inhibiting apoptosis and stimulating crypt cell proliferation (4).Vitamin A is a fat-soluble vitamin required for a number of physiological activities. Retinyl esters (REs), animal-derived forms of vitamin A, are hydrolyzed into retinol before entering the absorptive epithelial cells. By contrast, β-carotene, a vegetable-derived form of vitamin A, is converted into retinal after entering the absorptive epithelial cells and is then reduced to retinol within the cells (5). The retinol thus produced binds to cellular retinol-binding protein II (CRBP II, gene symbol Rbp2) in absorptive epithelial cells, forming a retinol-CRBP II complex. This complex is esterified to REs by lecithin retinol acyltransferase (LRAT, gene symbol Lrat). REs are then discharged basolaterally into the lymphatic vessels as a component of chylomicrons and are delivered to ...

Single-Cell Analysis Reveals Regional Reprogramming During Adaptation to Massive Small Bowel Resection in Mice

“…Increased Apoa4 and Rbp2 expression following SBR has been previously described 21, 22, 23. Contrary to our findings, one of these studies reported no significant changes in ileal Fabp1 mRNA expression.…”

“…Contrary to our findings, one of these studies reported no significant changes in ileal Fabp1 mRNA expression. However, this study examined whole tissue preparations, rather than epithelium at single-cell resolution 23 . Thus, to validate the transcriptional changes revealed by our scRNA-seq analysis, we surveyed Fabp1 expression via RNA fluorescence in situ hybridization (RNA-FISH) on histological sections of sham and SBR animals at 7 and 70 days postsurgery, with the latter analysis designed to investigate whether the observed changes are stable, a property rarely investigated in the context of SBR.…”

“…In the context of this study, retinoid metabolism was of particular interest because it has been shown to play a key role in structural adaptation 21, 22, 23, 32, 33. Retinoids are derived from vitamin A, which must be obtained from the diet, 34 and are mostly absorbed in proximal SI 35 .…”

Single-Cell Analysis Reveals Regional Reprogramming during Adaptation to Massive Small Bowel Resection in Mice

“…Contrary to our findings, one of these studies reported no significant changes in ileal Fabp1 mRNA expression. However, this study examined whole tissue preparations, rather than epithelium at single-cell resolution 23 To further validate our findings, we performed quantitative immunofluorescence, western blotting, and qPCR for selected proteins and transcripts, including FABP1, FABP6, APOC3, Rbp2, and…”

Intestinal Transcriptome Analysis Reveals Soy Derivative-Linked Changes in Atlantic Salmon

“…Retinol-binding protein transports vitamin A from the liver to other tissues like the intestine (47). It has been reported that tissue injury during inflammation causes a reduction in the synthesis of retinol-binding protein (48).…”