| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Chen, Zhouji Graham, Mark J. Yoshino, Jun Finck, Brian N. Albert, Carolyn J. Soufi, Nisreen Brunt, Elizabeth M. Ford, David A. Hall, Angela M. Collier, Sara L. Mathews, James C. |
| Description |
Author Affiliation: Soufi N ( From the Departments of Pediatrics, Medicine, and.); Hall AM ( Medicine, and.); Chen Z ( Medicine, and.); Yoshino J ( Medicine, and.); Collier SL ( Medicine, and.); Mathews JC ( Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri 63110.); Brunt EM ( Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri 63110.); Albert CJ ( the Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, Missouri 63104, and.); Graham MJ ( ISIS Pharmaceuticals Inc., Carlsbad, California 92008.); Ford DA ( the Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, Missouri 63104, and.); Finck BN ( Medicine, and bfinck@dom.wustl.edu.) |
| Abstract |
Abnormalities in hepatic lipid metabolism and insulin action are believed to play a critical role in the etiology of nonalcoholic steatohepatitis. Monoacylglycerol acyltransferase (MGAT) enzymes convert monoacylglycerol to diacylglycerol, which is the penultimate step in one pathway for triacylglycerol synthesis. Hepatic expression of Mogat1, which encodes an MGAT enzyme, is increased in the livers of mice with hepatic steatosis, and knocking down Mogat1 improves glucose metabolism and hepatic insulin signaling, but whether increased MGAT activity plays a role in the etiology of nonalcoholic steatohepatitis is unclear. To examine this issue, mice were placed on a diet containing high levels of trans fatty acids, fructose, and cholesterol (HTF-C diet) or a low fat control diet for 4 weeks. Mice were injected with antisense oligonucleotides (ASOs) to knockdown Mogat1 or a scrambled ASO control for 12 weeks while remaining on diet. The HTF-C diet caused glucose intolerance, hepatic steatosis, and induced hepatic gene expression markers of inflammation, macrophage infiltration, and stellate cell activation. Mogat1 ASO treatment, which suppressed Mogat1 expression in liver and adipose tissue, attenuated weight gain, improved glucose tolerance, improved hepatic insulin signaling, and decreased hepatic triacylglycerol content compared with control ASO-treated mice on HTF-C chow. However, Mogat1 ASO treatment did not reduce hepatic diacylglycerol, cholesterol, or free fatty acid content; improve histologic measures of liver injury; or reduce expression of markers of stellate cell activation, liver inflammation, and injury. In conclusion, inhibition of hepatic Mogat1 in HTF-C diet-fed mice improves hepatic metabolic abnormalities without attenuating liver inflammation and injury. |
| ISSN |
00219258 |
| e-ISSN |
1083351X |
| Journal |
Journal of Biological Chemistry |
| Issue Number |
43 |
| Volume Number |
289 |
| Language |
English |
| Publisher |
American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date |
2014-10-24 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Acyltransferases Antagonists & Inhibitors Inflammation Pathology Liver Metabolism Adipose Tissue Drug Effects Enzymology Adiposity Animals Biological Markers Diet Diglycerides Fatty Acids Fatty Liver Gene Expression Regulation Gene Knockdown Techniques Glucose Glucose Tolerance Test Hepatic Stellate Cells Homeostasis Leukocytes Lipogenesis Genetics Mice, Inbred C57BL Mice, Obese Oligonucleotides, Antisense Administration & Dosage Pharmacology Oxidation-Reduction Triglycerides Weight Gain Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Cell Biology Biochemistry Molecular Biology |
