|
| Status |
Public on Jan 30, 2020 |
| Title |
Removing a Double Bond from Ceramides Ameliorates Insulin Resistance and Hepatic Steatosis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Ceramides contribute to the lipotoxicity that underlies diabetes, hepatic steatosis, and heart disease. By genetically engineering mice, we deleted the enzyme dihydroceramide desaturase-1 (DES1) which inserts a conserved double bond into the backbone of ceramides and other predominant sphingolipids. Ablation of DES1 from whole animals, or tissue-specific deletion in the liver, and/or adipose tissue resolved hepatic steatosis and insulin resistance in mice caused by leptin deficiency or obesogenic diets. Mechanistic studies revealed new ceramide actions that promoted lipid uptake and storage and impaired glucose utilization, none of which could be recapitulated by (dihydro)ceramides that lacked the critical double bond. These studies suggest that inhibition of DES1 may provide a means of treating hepatic steatosis and cardiometabolic disorders.
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| |
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| Overall design |
Livers isolated from Control and Liver specific Degs1 knockout mice following either normal chow or high fat diet feeding
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| |
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| Contributor(s) |
Summers SA, Chaurasia B |
| Citation(s) |
31273070 |
| |
| Submission date |
May 31, 2019 |
| Last update date |
Jan 30, 2020 |
| Contact name |
Chris Stubben |
| Organization name |
Huntsman Cancer Institute
|
| Department |
University of Utah
|
| Street address |
2000 Cir of Hope Dr
|
| City |
Salt Lake City |
| State/province |
Utah |
| ZIP/Postal code |
84103 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA545734 |
| SRA |
SRP200061 |
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