In a new study appearing on August 1 in The Journal of Clinical Investigation, Yo-ichi Nabeshima and colleagues from Kyoto University generated and analyzed beta Klotho-null mice to investigate its function.
The researchers found that beta Klotho is important for cholesterol and bile acid metabolism. Serum cholesterol levels of beta Klotho-null mice were reduced compared with the wild type mice. Moreover, production and excretion of bile acids were dramatically elevated in beta Klotho-null mice.
The expression of two key bile acid synthesis genes, the nuclear receptors regulating these genes, and the liver circulation was intact. However, the negative feedback suppression of one bile acid synthesis gene was significantly impaired. Interestingly, the loss of beta Klotho also provided some benefits to the mice including absence of gallstone formation, and control of body weight and cholesterol levels, suggesting future clinical potential of the beta Klotho system.
In a related commentary, Antonio Moschetta and Steven Kliewer write, "These findings highlight the central role of beta Klotho in bile acid homeostasis and raise the possibility that this protein could be a pharmacological treatment for gallstones."
TITLE: Impaired negative feedback suppression of bile acid synthesis in mice lacking beta Klotho
Kyoto University Graduate School of Medicine, Kyoto Japan
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