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Increased expression of ileal apical sodium-dependent bile acid transporter in postpartum rats
Aldo D Mottino1, Tim Hoffman, Paul A Dawson
1Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536-0305, USA.
Insights
Lactating rats show increased expression of the apical ileal sodium-dependent bile acid transporter (ASBT) in the small intestine. This enhances bile acid reclamation during peak lactation.
Area of Science:
- Physiology
- Gastroenterology
- Endocrinology
Background:
- Bile acid homeostasis is crucial for nutrient absorption and metabolic regulation.
- The apical ileal sodium-dependent bile acid transporter (ASBT) plays a key role in intestinal bile acid reabsorption.
- Pregnancy and lactation induce significant physiological changes that can impact nutrient transport.
Purpose of the Study:
- To investigate the regulation of ASBT expression and activity in the rat small intestine during pregnancy and postpartum lactation.
- To determine if ASBT-mediated bile acid transport is altered during the physiological demands of lactation.
Main Methods:
- Western blot analysis of brush border membrane vesicles (BBMV) to quantify ASBT protein expression.
- Analysis of ASBT mRNA levels to assess transcriptional regulation.
- Intestinal loop model to measure taurocholate (TC) absorption in vivo.
Main Results:
- ASBT expression was maximal in the distal ileum across all groups.
- ASBT protein expression significantly increased in lactating rats (12 and 21 days postpartum) compared to controls.
- Posttranscriptional regulation of ASBT was suggested by mRNA analysis.
- Taurolcholate (TC) transport and absorption increased significantly in the proximal ileum of lactating rats.
Conclusions:
- ASBT expression and function are significantly upregulated in the rat ileum during peak lactation.
- Increased ASBT-mediated bile acid reclamation contributes to maintaining bile acid homeostasis during lactation.
- These adaptations support the increased metabolic demands associated with milk production.
Abstract:
The expression and activity of the apical ileal sodium-dependent bile acid transporter (asbt) was examined in the small intestine of control, pregnant, and lactating postpartum rats 2, 12, and 21 days after delivery. Western blot analysis of brush border membrane vesicles (BBMV) prepared from different regions of the small intestine demonstrated that expression of asbt was maximal in the most distal segments for all experimental groups, was not substantially affected in pregnant and 2-day postpartum rats, and was significantly increased in 12- and 21-day postpartum rats. Analysis of mRNA suggested that asbt protein was regulated at the posttranscriptional level in postpartum rats. Increased expression of asbt protein postpartum was maximal (approximately 2-fold) in the proximal region of the ileum, consistent with a 60% increase in taurocholate (TC) transport in BBMV from the proximal ileum in 14- to 21-day postpartum rats relative to control rats. Absorption of TC, determined from the intact proximal ileum using an intestinal loop model, demonstrated a 30% increase in TC uptake per unit weight of tissue in 14- to 21-day postpartum rats relative to control rats. Together with the marked increase in intestinal mass observed at peak lactation, these data indicate a significant increase in asbt-mediated reclamation of bile acids in the intestine of lactating rats.