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Bile Acid is a Key Stimulus of Liver Regeneration

Normal mice fed cholic acid have 30 percent increase in liver size

FRIDAY, April 14 (HealthDay News) -- Liver regeneration is triggered by a "homeotrophic" response where hepatocytes sense higher levels of bile acids and increase bile acid signaling through the nuclear hormone receptor FXR, according to a report in the April 14 issue of Science.

The mammalian liver has tremendous potential for regrowth, however, the stimulus responsible for triggering regeneration has been unclear. Now, Wendong Huang, Ph.D., from Baylor College of Medicine in Houston, Texas, and colleagues used a mouse model of liver damage to help decipher the primary regenerative stimulus.

First, the investigators found that feeding normal mice a five-day, mild diet containing 0.2 percent cholic acid, a bile acid, caused a 30 percent increase in liver size compared with controls. Then using partial hepatectomy to stimulate the liver damage response, the authors found activation of the bile acid receptor, FXR, occurred during liver regeneration. Reducing bile acid levels failed to stimulate FXR signaling in vitro, and liver regeneration was slower in FXR-deficient mice. FXR activation was also found to slow down potentially toxic bile acid production.

"We propose that FXR activation by increased bile acid flux is a signal of decreased functional capacity of the liver," the authors write. "FXR, and possibly other nuclear receptors, may promote homeostasis not only by regulating expression of appropriate metabolic target genes but also by driving homeotrophic liver growth."

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