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| Status |
Public on Apr 07, 2009 |
| Title |
Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Hepatic metabolic derangements are key components in the development of fatty liver, insulin resistance, and atherosclerosis. SIRT1, a NAD+-dependent protein deacetylase, is an important regulator of energy homeostasis in response to nutrient availability. Here we demonstrate that hepatic SIRT1 regulates fatty acid metabolism by positively regulating PPAR-alpha. Hepatocyte-specific deletion of SIRT1 impairs PPAR-alpha signaling and decreased fatty acid beta-oxidation in the liver. When challenged with a high-fat diet, liver-specific SIRT1 knockout mice develop hepatic steatosis, hepatic inflammation, and endoplasmic reticulum stress. Taken together, our data indicate that SIRT1 plays a vital role in the regulation of hepatic lipid homeostasis.
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| Overall design |
ix Lox control and six Liver-specific SIRT1 KO (SIRT1 LKO) mice in 95% C57BL/6 background were fed ad libitum with free access to water and food. They were then sacrificed at 4:00pm to analyze PPAR-alpha mediated phenotypes under physiologically relevant conditions. Livers from these mice were then dissected and RNA was isolated with a Qiagen RNA easy mini kit with on-column DNAseI treatment. RNA quality was validated with the Agilent 2100 Bioanalyzer in the microarray facility. RNA samples were then pooled with 2 animals/replicate and analyzed by Agilent Whole Mouse arrays. Data are generated by the Rosetta Resolver Error Model.
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| Contributor(s) |
Purushotham A, Xu Q, Li X, Collins J |
| Citation(s) |
19356714 |
| |
| Submission date |
Feb 20, 2009 |
| Last update date |
Jan 12, 2017 |
| Contact name |
NIEHS Microarray Core |
| E-mail(s) |
microarray@niehs.nih.gov, liuliw@niehs.nih.gov
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| Organization name |
NIEHS
|
| Department |
DIR
|
| Lab |
Microarray Core
|
| Street address |
111 T.W. Alexander Drive
|
| City |
RTP |
| State/province |
NC |
| ZIP/Postal code |
27709 |
| Country |
USA |
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| Platforms (1) |
| GPL7202 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Probe Name version) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA111907 |
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