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| Status |
Public on Nov 05, 2014 |
| Title |
Inhibiting Monoacylglycerol Acyltransferase 1 Ameliorates Hepatic Metabolic Abnormalities, but not Inflammation and Injury in Mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Abnormalities in hepatic lipid metabolism are believed to play a critical role in the etiology of nonalcoholic steatohepatitis (NASH). Monoacylglycerol acyltransferase (MGAT) enzymes convert monoacylglycerol to diacylglycerol, which is the penultimate step in one pathway for triacylglycerol (TAG) 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 insulin sensitivity, but whether increased MGAT activity plays a role in the etiology of NASH is unclear. To examine the effects of knocking down Mogat1 in the liver on the development of NASH, C57BL/6 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 then injected with antisense oligonucleotides (ASO) to knockdown Mogat1 or a scrambled ASO control for 12 weeks while remaining on diet. 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, attenuated weight gain, improved glucose tolerance, and decreased hepatic TAG content compared to control ASO-treated mice on HTF-C chow. However, Mogat1 ASO treatment did not reduce hepatic DAG, 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 glucose tolerance and hepatic TAG accumulation without attenuating liver inflammation and injury.
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| Overall design |
Total RNA obtained from liver of 4 control vs. 4 Mogat1 ASO treated higf-fat diet (HFD) fed mice.
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| Contributor(s) |
Soufi N, Hall AM, Yoshino J, Collier SL, Mathews JC, Brunt EM, Albert CJ, Graham MJ, Ford DA, Finck BN |
| Citation(s) |
25213859 |
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| Submission date |
Aug 12, 2014 |
| Last update date |
Sep 15, 2023 |
| Contact name |
Jun Yoshino |
| E-mail(s) |
jyoshino@med.shimane-u.ac.jp
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| Organization name |
Faculty of Medicine, Shimane University
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| Street address |
89-1 Enya-cho
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| City |
Izumo |
| State/province |
Shimane |
| ZIP/Postal code |
693-8501 |
| Country |
Japan |
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| Platforms (1) |
| GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA258077 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE60349_RAW.tar |
15.8 Mb |
(http)(custom) |
TAR |
| GSE60349_non_normalized.txt.gz |
2.6 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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