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| Status |
Public on Aug 03, 2011 |
| Title |
Expression of Splicing Factor Genes is Reduced in Human Obesity and Contributes to Enhanced Lipogenesis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Alternative mRNA splicing provides transcript diversity and has been proposed to contribute to several human diseases. Here, we demonstrate that expression of genes regulating RNA processing is decreased in both liver and skeletal muscle of obese humans. To determine the metabolic impact of reduced splicing factor expression, we further evaluated the splicing factor, SFRS10, identified as down-regulated in obese human liver and skeletal muscle and in high fat fed rodents. siRNA-mediated reductions in SFRS10 expression induced lipogenesis and lipid accumulation in cultured hepatocytes. Moreover, SFRS10 heterozygous mice have both increased hepatic lipogenic gene expression and hypertriglyceridemia. We also demonstrate that LPIN1, a key regulator of lipid metabolism, is a splicing target of SFRS10, with reduced SFRS10 levels favoring the lipogenic β isoform of LPIN1. Importantly, LPIN1β-specific siRNA abolished the lipogenic effects of decreased SFRS10 expression. Together, our results indicate reduced expression of SFRS10 alters LPIN1 splicing and induces lipogenesis, demonstrating that reduced splicing factor expression observed in human tissues may contribute to metabolic phenotypes associated with human obesity.
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| Overall design |
Skeletal muscle samples were obtained from 10 lean control subjects and 7 obese subjects with either IGT or DM2 undergoing elective cholecystectomy. Data for liver samples presented in the same manuscript are available at GEO GSE15653. In this analysis RNA was isolated for cRNA preparation and hybridized to Affymetrix Human Genome U133 Plus 2.0 microarrays.
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| Contributor(s) |
Pihlajamäki J, Lerin C, Itkonen P, Boes T, Floss T, Dearie F, Crunkhorn S, Burak F, Jimenez-Chillaron JC, Kuulasmaa T, Miettinen P, Park PJ, Nasser I, Zhao Z, Zhang Z, Xu Y, Wurst W, Stamm S, Goldfine AB, Laakso M, Patti ME |
| Citation(s) |
21803291 |
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| Submission date |
Jun 18, 2010 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Mary Elizabeth Patti |
| E-mail(s) |
mary.elizabeth.patti@joslin.harvard.edu
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| Phone |
6177351966
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| Fax |
6177322593
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| Organization name |
Joslin Diabetes Center
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| Department |
Research Division
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| Street address |
1 Joslin Place
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (17)
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| Relations |
| BioProject |
PRJNA128545 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE22435_RAW.tar |
143.5 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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