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Open Access Green as soon as Postprint is submitted to ZB.
Expression of the splicing factor gene SFRS10 is reduced in human obesity and contributes to enhanced lipogenesis.
Cell Metab. 14, 208-218 (2011)
Alternative mRNA splicing provides transcript diversity and may contribute to human disease. We demonstrate that expression of several genes regulating RNA processing is decreased in both liver and skeletal muscle of obese humans. We evaluated a representative splicing factor, SFRS10, downregulated in both obese human liver and muscle and in high-fat-fed mice, and determined metabolic impact of reduced expression. SFRS10-specific siRNA induces lipogenesis and lipid accumulation in hepatocytes. Moreover, Sfrs10 heterozygous mice have increased hepatic lipogenic gene expression, VLDL secretion, and plasma triglycerides. We demonstrate that LPIN1, a key regulator of lipid metabolism, is a splicing target of SFRS10; reduced SFRS10 favors the lipogenic β isoform of LPIN1. Importantly, LPIN1β-specific siRNA abolished lipogenic effects of decreased SFRS10 expression. Together, our results indicate that reduced expression of SFRS10, as observed in tissues from obese humans, alters LPIN1 splicing, induces lipogenesis, and therefore contributes to metabolic phenotypes associated with obesity.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Genome-wide association; Pre-messenger-RNA; Adipose-tissue; Insulln-resistance; Skeletal-muscle; Diabetic mice; Lipin; Metabolism; Receptor; Protein
ISSN (print) / ISBN
1550-4131
e-ISSN
1932-7420
Journal
Cell Metabolism
Quellenangaben
Volume: 14,
Issue: 2,
Pages: 208-218
Publisher
Elsevier
Reviewing status
Peer reviewed
Institute(s)
Institute of Developmental Genetics (IDG)