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Story ideas from the Journal of Lipid Research
Date:12/3/2007

i.vanleuven@amc.uva.nl">s.i.vanleuven@amc.uva.nl

Breaking the Vicious Cycle of Bile Acid Disorders

Researchers have found a potential new and improved avenue for treating defective bile acid absorption, a primary contributor to chronic diarrhea.

Liver-produced bile acids are intestinal detergents that break apart fats for easier absorption. Normally, most of the bile acids also reabsorb, but during certain conditions (e.g. infection or short bowel syndrome) excess bile acids enter the colon and impair water absorption, leading to diarrhea.

What makes bile acid malabsorption particularly insidious is that if enough bile acids dont reabsorb, the liver churns out even more acids to compensate, which produces even more problems.

Antonio Moschetta and colleagues targeted the intestinal receptor FXR to see if they could break this vicious cycle. When bile acids reenter intestinal cells, they attach to FXR, which in turn activates a hormone called FGF15 to helps suppress bile acid production.

The researchers fed a synthetic FXR target to engineered mice with defective bile absorption and found that treatment increased the FGF15 activation and reduced the total amount of bile acids present in both the liver and feces. They achieved similar results if they directly introduced FGF15 into the livers of the mice.

Moschetta and colleagues note that FXR drugs would be more beneficial than current treatments that use resins to sequester bile acids, which alleviates the diarrhea but doesnt solve the underlying absorption problem.

CORRESPONDING AUTHOR: David Mangelsdorf, Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas; Phone: 214-645-5957, email: davo.mango@utsouthwestern.edu


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Contact: Nick Zagorski
nzagorski@asbmb.org
American Society for Biochemistry and Molecular Biology
Source:Eurekalert

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