Inhibiting glycosphingolipid synthesis ameliorates hepatic steatosis in obese mice Potential conflict of interest: Nothing to report.
dc.contributor.author | Zhao, Hongmei | en_US |
dc.contributor.author | Przybylska, Malgorzata | en_US |
dc.contributor.author | Wu, I-Huan | en_US |
dc.contributor.author | Zhang, Jinhua | en_US |
dc.contributor.author | Maniatis, Panagiotis | en_US |
dc.contributor.author | Pacheco, Joshua | en_US |
dc.contributor.author | Piepenhagen, Peter | en_US |
dc.contributor.author | Copeland, Diane | en_US |
dc.contributor.author | Arbeeny, Cynthia | en_US |
dc.contributor.author | Shayman, James A. | en_US |
dc.contributor.author | Aerts, Johannes M. | en_US |
dc.contributor.author | Jiang, Canwen | en_US |
dc.contributor.author | Cheng, Seng H. | en_US |
dc.contributor.author | Yew, Nelson S. | en_US |
dc.date.accessioned | 2009-07-06T15:39:14Z | |
dc.date.available | 2010-09-01T19:24:06Z | en_US |
dc.date.issued | 2009-07 | en_US |
dc.identifier.citation | Zhao, Hongmei; Przybylska, Malgorzata; Wu, I-Huan; Zhang, Jinhua; Maniatis, Panagiotis; Pacheco, Joshua; Piepenhagen, Peter; Copeland, Diane; Arbeeny, Cynthia; Shayman, James A.; Aerts, Johannes M.; Jiang, Canwen; Cheng, Seng H.; Yew, Nelson S. (2009). "Inhibiting glycosphingolipid synthesis ameliorates hepatic steatosis in obese mice Potential conflict of interest: Nothing to report. ." Hepatology 50(1): 85-93. <http://hdl.handle.net/2027.42/63066> | en_US |
dc.identifier.issn | 0270-9139 | en_US |
dc.identifier.issn | 1527-3350 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/63066 | |
dc.description.abstract | Steatosis in the liver is a common feature of obesity and type 2 diabetes and the precursor to the development of nonalcoholic steatohepatitis (NASH), cirrhosis, and liver failure. It has been shown previously that inhibiting glycosphingolipid (GSL) synthesis increases insulin sensitivity and lowers glucose levels in diabetic rodent models. Here we demonstrate that inhibiting GSL synthesis in ob/ob mice not only improved glucose homeostasis but also markedly reduced the development of hepatic steatosis. The ob/ob mice were treated for 7 weeks with a specific inhibitor of glucosylceramide synthase, the initial enzyme involved in the synthesis of GSLs. Besides lowering glucose and hemoglobin A1c (HbA1c) levels, drug treatment also significantly reduced the liver/body weight ratio, decreased the accumulation of triglycerides, and improved several markers of liver pathology. Drug treatment reduced liver glucosylceramide (GL1) levels in the ob/ob mouse. Treatment also reduced the expression of several genes associated with hepatic steatosis, including those involved in lipogenesis, gluconeogenesis, and inflammation. In addition, inhibiting GSL synthesis in diet-induced obese mice both prevented the development of steatosis and partially reversed preexisting steatosis. Conclusion: These data indicate that inhibiting GSL synthesis ameliorates the liver pathology associated with obesity and diabetes, and may represent a novel strategy for treating fatty liver disease and NASH. (H EPATOLOGY 2009.) | en_US |
dc.format.extent | 1687813 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Hepatology | en_US |
dc.title | Inhibiting glycosphingolipid synthesis ameliorates hepatic steatosis in obese mice Potential conflict of interest: Nothing to report. | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Internal Medicine and Specialties | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Nephrology Division, Department of Internal Medicine, University of Michigan, Ann Arbor, MI | en_US |
dc.contributor.affiliationother | Genzyme Corp., Framingham, MA | en_US |
dc.contributor.affiliationother | Genzyme Corp., Framingham, MA | en_US |
dc.contributor.affiliationother | Genzyme Corp., Framingham, MA | en_US |
dc.contributor.affiliationother | Genzyme Corp., Framingham, MA | en_US |
dc.contributor.affiliationother | Genzyme Corp., Framingham, MA | en_US |
dc.contributor.affiliationother | Genzyme Corp., Framingham, MA | en_US |
dc.contributor.affiliationother | Genzyme Corp., Framingham, MA | en_US |
dc.contributor.affiliationother | Genzyme Corp., Framingham, MA | en_US |
dc.contributor.affiliationother | Genzyme Corp., Framingham, MA | en_US |
dc.contributor.affiliationother | Department of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlands | en_US |
dc.contributor.affiliationother | Genzyme Corp., Framingham, MA | en_US |
dc.contributor.affiliationother | Genzyme Corp., Framingham, MA ; fax: 508-661-8812 ; Genzyme Corp., 49 New York Avenue, Framingham, MA 01701-9322 | en_US |
dc.contributor.affiliationother | Genzyme Corp., Framingham, MA | en_US |
dc.identifier.pmid | 19444873 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/63066/1/22970_ftp.pdf | |
dc.identifier.doi | 10.1002/hep.22970 | en_US |
dc.identifier.source | Hepatology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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