Researchers at the University of Pittsburgh, Pittsburgh, PA have demonstrated that the Wnt/β-catenin signaling pathway plays a key role in hepatic bile acid and cholesterol homeostasis as well as helps protect the adult liver against metabolic stress.
Their report can be found in the February 2010 issue of The American Journal of Pathology.
The liver has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion. The liver is the primary organ involved in lipid metabolism, and liver dysfunction often results in accumulation of lipids within the liver (steatosis). The Wnt/β-catenin signaling pathway is involved in liver development, regeneration, and liver cancer; however, its role in non-cancerous liver disease has not been well characterized.
To determine the effects of β-catenin-deficiency on lipid accumulation and injury in the liver, Behari et al induced dietary-caused liver injury in both wild-type and β-catenin-deficient mice. They found that β-catenin-deficient mice developed higher levels of lipid accumulation and fibrosis as well as accumulated higher liver cholesterol levels than wild-type mice. Furthermore, β-catenin-deficient mice had higher levels of bile acid, which aid in digestion of dietary fat, despite lower expression of bile acid synthesis enzymes, suggesting defects in bile transport. These findings suggest that β-catenin signaling plays a key role in hepatic bile acid and cholesterol homeostasis as well as in protecting against metabolic stress.
The findings by Behari and colleagues "suggest that β-catenin is an additional player in the complex network of nuclear receptors that regulates bile acid and lipid metabolism in the liver. Identifying the interactions between these receptors and β-catenin may help elucidate additional regulatory mechanisms that could have potential therapeutic implications in both cholestatic and metabolic liver diseases."
- Behari J, Yeh T-H, Krauland L, Otruba W, Cieply B, Hauth B, Apte U, Wu T, Evans R, Monga SPS. Liver-Specific %u03B2-Catenin Knockout Mice Exhibit Defective Bile Acid and Cholesterol Homeostasis and Increased Susceptibility to Diet-Induced Steatohepatitis. American Journal of Pathology, 2010; 176: 744-753 DOI: 10.2353/ajpath.2010.090667
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