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Expression of the Splicing Factor Gene SFRS10 is Reduced in Human Obesity and Contributes to Enhanced Lipogenesis
- Source :
- Cell Metab. 14, 208-218 (2011), Cell metabolism 14(2), 208-218 (2011). doi:10.1016/j.cmet.2011.06.007
- Publication Year :
- 2011
-
Abstract
- 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.
- Subjects :
- Male
Very low-density lipoprotein
metabolism [Muscle, Skeletal]
Physiology
RNA-binding protein
Mice
0302 clinical medicine
genetics [Obesity]
Genome-wide association
Pre-messenger-RNA
Adipose-tissue
Insulln-resistance
Skeletal-muscle
Diabetic mice
Lipin
Metabolism
Receptor
Protein
Gene expression
blood [Lipids]
genetics [RNA-Binding Proteins]
genetics [Nerve Tissue Proteins]
2. Zero hunger
Regulation of gene expression
0303 health sciences
Mice, Inbred ICR
Serine-Arginine Splicing Factors
RNA-Binding Proteins
Middle Aged
Lipids
TRA2B protein, human
Liver
030220 oncology & carcinogenesis
Lipogenesis
RNA splicing
biosynthesis [Lipids]
Female
genetics [Phosphatidate Phosphatase]
Adult
medicine.medical_specialty
genetics [Lipogenesis]
RNA Splicing
Phosphatidate Phosphatase
Mice, Transgenic
Nerve Tissue Proteins
Biology
Article
biosynthesis [RNA-Binding Proteins]
03 medical and health sciences
Splicing factor
Internal medicine
ddc:570
Cell Line, Tumor
metabolism [Obesity]
medicine
Animals
Humans
LPIN1 protein, human
Obesity
genetics [Lipids]
biosynthesis [Nerve Tissue Proteins]
Muscle, Skeletal
Molecular Biology
030304 developmental biology
Aged
Lipid metabolism
Cell Biology
Endocrinology
Gene Expression Regulation
metabolism [Liver]
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cell Metab. 14, 208-218 (2011), Cell metabolism 14(2), 208-218 (2011). doi:10.1016/j.cmet.2011.06.007
- Accession number :
- edsair.doi.dedup.....bfa29e0ff2ebe8f77da37a6a0ca17b8c