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

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • Subject Terms:
      Obesity*/metabolism ; Bile Acids and Salts*/metabolism ; Ileum*/metabolism ; Rats, Zucker* ; Intestinal Absorption* ; Symporters*/metabolism ; Symporters*/genetics ; Organic Anion Transporters, Sodium-Dependent*/metabolism ; Organic Anion Transporters, Sodium-Dependent*/genetics; Animals ; Rats ; Male ; Intestinal Mucosa/metabolism ; Receptors, Cytoplasmic and Nuclear/metabolism ; Receptors, Cytoplasmic and Nuclear/genetics
    • 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 3 H-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.
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    • Grant Information:
      DK-67420 National Institute of Health; DK-108054 National Institute of Health; P20GM121299-01A1 National Institute of Health; BX003443-01 Veteran's Administration Merit Review
    • Contributed Indexing:
      Keywords: apical sodium bile acid transporter; bile acids; farnesoid X receptor; intestinal physiology; metabolic disorders; obesity; obesity-related risk factors
    • Accession Number:
      0 (Bile Acids and Salts)
      0 (Symporters)
      145420-23-1 (sodium-bile acid cotransporter)
      0 (Organic Anion Transporters, Sodium-Dependent)
      0C5V0MRU6P (farnesoid X-activated receptor)
      0 (Receptors, Cytoplasmic and Nuclear)
    • Publication Date:
      Date Created: 20241109 Date Completed: 20241109 Latest Revision: 20241116
    • Publication Date:
      20241116
    • Accession Number:
      PMC11547122
    • Accession Number:
      10.3390/ijms252111452
    • Accession Number:
      39519005