Expression of the splicing factor gene SFRS10 is reduced in human obesity and contributes to enhanced lipogenesis

Jussi Pihlajamäki, Carles Lerin, Paula Itkonen, Tanner Boes, Thomas Floss, Joshua Schroeder, Farrell Dearie, Sarah Crunkhorn, Furkan Burak, Josep C. Jimenez-Chillaron, Tiina Kuulasmaa, Pekka Miettinen, Peter J. Park, Imad Nasser, Zhenwen Zhao, Zhaiyi Zhang, Yan Xu, Wolfgang Wurst, Hongmei Ren, Andrew J. Morris & 4 others Stefan Stamm, Allison B. Goldfine, Markku Laakso, Mary Elizabeth Patti

Research output: Contribution to journalArticle

62 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)208-218
Number of pages11
JournalCell Metabolism
Volume14
Issue number2
DOIs
StatePublished - Aug 3 2011

Fingerprint

Lipogenesis
Obesity
Small Interfering RNA
Genes
Liver
Gene Expression
Alternative Splicing
Lipid Metabolism
Hepatocytes
Protein Isoforms
Skeletal Muscle
Triglycerides
Down-Regulation
Fats
RNA
Phenotype
Lipids
Muscles
Messenger RNA
RNA Splicing Factors

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Pihlajamäki, J., Lerin, C., Itkonen, P., Boes, T., Floss, T., Schroeder, J., ... Patti, M. E. (2011). Expression of the splicing factor gene SFRS10 is reduced in human obesity and contributes to enhanced lipogenesis. Cell Metabolism, 14(2), 208-218. https://doi.org/10.1016/j.cmet.2011.06.007

Expression of the splicing factor gene SFRS10 is reduced in human obesity and contributes to enhanced lipogenesis. / Pihlajamäki, Jussi; Lerin, Carles; Itkonen, Paula; Boes, Tanner; Floss, Thomas; Schroeder, Joshua; Dearie, Farrell; Crunkhorn, Sarah; Burak, Furkan; Jimenez-Chillaron, Josep C.; Kuulasmaa, Tiina; Miettinen, Pekka; Park, Peter J.; Nasser, Imad; Zhao, Zhenwen; Zhang, Zhaiyi; Xu, Yan; Wurst, Wolfgang; Ren, Hongmei; Morris, Andrew J.; Stamm, Stefan; Goldfine, Allison B.; Laakso, Markku; Patti, Mary Elizabeth.

In: Cell Metabolism, Vol. 14, No. 2, 03.08.2011, p. 208-218.

Research output: Contribution to journalArticle

Pihlajamäki, J, Lerin, C, Itkonen, P, Boes, T, Floss, T, Schroeder, J, 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, Ren, H, Morris, AJ, Stamm, S, Goldfine, AB, Laakso, M & Patti, ME 2011, 'Expression of the splicing factor gene SFRS10 is reduced in human obesity and contributes to enhanced lipogenesis', Cell Metabolism, vol. 14, no. 2, pp. 208-218. https://doi.org/10.1016/j.cmet.2011.06.007
Pihlajamäki, Jussi ; Lerin, Carles ; Itkonen, Paula ; Boes, Tanner ; Floss, Thomas ; Schroeder, Joshua ; Dearie, Farrell ; Crunkhorn, Sarah ; Burak, Furkan ; Jimenez-Chillaron, Josep C. ; Kuulasmaa, Tiina ; Miettinen, Pekka ; Park, Peter J. ; Nasser, Imad ; Zhao, Zhenwen ; Zhang, Zhaiyi ; Xu, Yan ; Wurst, Wolfgang ; Ren, Hongmei ; Morris, Andrew J. ; Stamm, Stefan ; Goldfine, Allison B. ; Laakso, Markku ; Patti, Mary Elizabeth. / Expression of the splicing factor gene SFRS10 is reduced in human obesity and contributes to enhanced lipogenesis. In: Cell Metabolism. 2011 ; Vol. 14, No. 2. pp. 208-218.
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AU - Schroeder, Joshua

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AU - Wurst, Wolfgang

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AU - Morris, Andrew J.

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AU - Laakso, Markku

AU - Patti, Mary Elizabeth

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