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. 2024 Oct 25;25(21):11452.
doi: 10.3390/ijms252111452.

Novel Expression of Apical Bile Acid Transport (ASBT) More Proximally Than Distal Ileum Contributing to Enhanced Intestinal Bile Acid Absorption in Obesity

Shanmuga Sundaram  1 , Arunkumar Jagadeesan  1 , Raja Singh Paulraj  1 , Uma Sundaram  1 , Subha Arthur  1
Affiliations

Novel Expression of Apical Bile Acid Transport (ASBT) More Proximally Than Distal Ileum Contributing to Enhanced Intestinal Bile Acid Absorption in Obesity

Shanmuga Sundaram et al. Int J Mol Sci. .

Abstract

Dietary lipid absorption is facilitated by bile acids. In the Zucker rat (ZR) model of obesity, bile acid absorption, mediated by the apical sodium bile acid transporter (ASBT), was increased in villus cells from the distal ileum. However, whether ASBT may be de novo expressed more proximally in the small intestine during obesity to facilitate additional bile acid absorption is not known. For this, starting from the end of the ileum to the mid jejunum, caudal-orally, five intestinal segments of equal length (S1-S5) were separated from lean and obese ZRs (LZR and OZR). Intestinal mucosa obtained from these segments were used for total RNA extraction, RT-qPCR and 3H-TCA uptake. The results showed that bile acid absorption along with the mRNA expression of ASBT and FXR progressively decreased caudal-orally in both LZRs and OZRs but was significantly higher in all small intestinal segments in OZRs. The expression of GATA4 was absent in the distal ileum (S1) in both LZRs and OZRs, but steadily increased along the proximal length in both. However, this steady increase was significantly reduced in the comparative obese proximal intestinal segments S2, S3, S4 and S5. The expressions of bile acid-activated G-protein-coupled bile acid receptor TGR5 and S1PR2 were unaltered in segments S1-S4 but were significantly increased in OZR S5. The paradigm changing observation of this study is that ASBT is expressed more proximally in the small intestine in obesity. This likely increases overall bile acid absorption and thereby lipid absorption in the proximal small intestine in obesity.

Keywords: apical sodium bile acid transporter; bile acids; farnesoid X receptor; intestinal physiology; metabolic disorders; obesity; obesity-related risk factors.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
3H-TCA uptake was significantly higher in all intestinal segments in OZRs compared to their relative segments in LZRs.
Figure 2
Figure 2
Total bile acid levels were significantly decreased in the intestinal content obtained from the (A) distal ileum and the (B) cecum in OZRs compared to LZRs.
Figure 3
Figure 3
(A) ASBT expression was significantly increased in all segments along the caudal-oral length of the small intestine in obesity. (B) FXR mRNA expression was highest in the distal ileal segments (S1) and decreased along the caudal-oral length of small intestine in both LZRs and OZRs. However, compared to LZR small intestinal segments, FXR expression was increased in all segments in OZRs.
Figure 4
Figure 4
GATA4 mRNA expression was absent in the distal ileum and increased along the caudal-oral length as expected in LZRs and OZRs. However, its expression was decreased in proximal segments in OZRs compared to LZRs.
Figure 5
Figure 5
mRNA expression of bile acid receptors (A) TGR5 and (B) S1PR2 were increased in mid-jejunal segments (S5) of OZRs compared to LZRs.
Figure 6
Figure 6
Illustration of segmental separation of small intestine to study alterations in the distribution of ASBT expression and its regulatory proteins.
See this image and copyright information in PMC

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