@article {152921,
	title = {Expression of the splicing factor gene SFRS10 is reduced in human obesity and contributes to enhanced lipogenesis.},
	journal = {Cell Metab},
	volume = {14},
	number = {2},
	year = {2011},
	month = {2011 Aug 3},
	pages = {208-18},
	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.

},
	keywords = {Adult, Aged, Animals, Cell Line, Tumor, Female, Gene Expression Regulation, Humans, Lipids, Lipogenesis, Liver, Male, Mice, Mice, Inbred ICR, Mice, Transgenic, Middle Aged, Muscle, Skeletal, Nerve Tissue Proteins, Obesity, Phosphatidate Phosphatase, RNA Splicing, RNA-Binding Proteins},
	issn = {1932-7420},
	doi = {10.1016/j.cmet.2011.06.007},
	author = {Pihlajam{\"a}ki, Jussi and Lerin, Carles and Itkonen, Paula and Boes, Tanner and Floss, Thomas and Schroeder, Joshua and Dearie, Farrell and Crunkhorn, Sarah and Burak, Furkan and Jimenez-Chillaron, Josep C and Kuulasmaa, Tiina and Miettinen, Pekka and <b>Park, Peter J</b> and Nasser, Imad and Zhao, Zhenwen and Zhang, Zhaiyi and Xu, Yan and Wurst, Wolfgang and Ren, Hongmei and Morris, Andrew J and Stamm, Stefan and Goldfine, Allison B and Laakso, Markku and Patti, Mary Elizabeth}
}
