Potential conflict of interest: Nothing to report.
Article first published online: 31 OCT 2012
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 56, Issue 5, page 2009, November 2012
How to Cite
Tanaka, N. and Gonzalez, F. J. (2012), Reply:. Hepatology, 56: 2009. doi: 10.1002/hep.25811
- Issue published online: 31 OCT 2012
- Article first published online: 31 OCT 2012
- Manuscript Accepted: 22 APR 2012
We thank Drs. Gabbi and Gustafsson for their interest in our study on serum metabolomic analysis of nonalcoholic steatohepatitis (NASH) in mice.1 We measured the hepatic contents of taurocholate and tauro-β-muricholate using ultraperformance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry. However, the hepatic levels of these bile acids were not decreased in mice treated for 2 weeks with a methionine- and choline-deficient (MCD) diet (Fig. 1). Although changes in expression of the canalicular bile acid transporters were not detected, hepatic bile excretion might be decreased to some degree. When hepatic bile acid levels are altered, the expression of small heterodimer partner (Shp) may be changed accordingly to maintain hepatic bile acid levels. Indeed, the levels of Shp mRNA were decreased by MCD treatment, even in the absence of a significant decrease in hepatic bile acid content (Fig. 2). These findings suggest an abnormal response of transcription factors and their target genes associated with bile acid homeostasis, and thus we propose a disruption of bile acid homeostasis during the course of NASH where proinflammatory cytokines and cellular stress may disrupt bile acid homeostasis, causing a vicious cycle. Thus, we are generally in agreement with Drs. Gabbi and Gustafsson's view that clarification of the dynamic changes in bile acid homeostasis and the related transcriptional factors during NASH development might lead to new bile-modulating therapies for NASH.
- 1Disruption of phospholipid and bile acid homeostasis in mice with nonalcoholic steatohepatitis [published online ahead of print January 30, 2012]. HEPATOLOGY. doi: 10.1002/hep.25630., , , , .
Naoki Tanaka M.D., Ph.D*, Frank J. Gonzalez Ph.D.*, * Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD.