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Regulation of alternative splicing in obesity and weight loss.

Kaminska D, Pihlajamäki J - Adipocyte (2013)

Bottom Line: According to recent reports approximately 95-100% of human multi-exon genes undergo AS.This increases the amount of functionally different protein isoforms, and in some cases leads to metabolic diseases.Understanding of the molecular mechanisms behind the aberrantly spliced transcripts may also provide opportunities for new diagnostic approaches.

View Article: PubMed Central - PubMed

Affiliation: Institute of Public Health and Clinical Nutrition; University of Eastern Finland; Kuopio, Finland.

ABSTRACT
Alternative splicing (AS) is a mechanism by which multiple mRNA transcripts are generated from a single gene. According to recent reports approximately 95-100% of human multi-exon genes undergo AS. This increases the amount of functionally different protein isoforms, and in some cases leads to metabolic diseases. Herein we provide a brief overview of the basic aspects of splicing regulation in obesity and insulin resistance with specific examples. In addition, we review our recent findings demonstrating that weight loss regulates AS of TCF7L2 gene in both liver and adipose tissue, and that this splicing associates with changes in fatty acid and glucose metabolism. Future studies using global analysis of transcript variants and splicing regulators are needed for exploring the association of AS with metabolic alterations in obesity and type 2 diabetes (T2D). Understanding of the molecular mechanisms behind the aberrantly spliced transcripts may also provide opportunities for new diagnostic approaches.

No MeSH data available.


Related in: MedlinePlus

Figure 1. Proposed mechanisms for changes in alternative splicing in obesity. Changes in phosphorylation (p in the figure) and transcription of serine/arginine-rich splicing factors (SR in the figure) may alter splicing leading to protein isoforms with different function. These effects may interact with single nucleotide polymorphisms (SNPs) in critical intron-exon boundaries. Dashed arrows refer to our own recently published data in Cell Metabolism.24
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Figure 1: Figure 1. Proposed mechanisms for changes in alternative splicing in obesity. Changes in phosphorylation (p in the figure) and transcription of serine/arginine-rich splicing factors (SR in the figure) may alter splicing leading to protein isoforms with different function. These effects may interact with single nucleotide polymorphisms (SNPs) in critical intron-exon boundaries. Dashed arrows refer to our own recently published data in Cell Metabolism.24

Mentions: Although the exact pathways regulating the activity of regulatory proteins are only partially known, it is important to note that insulin signaling pathways lead to phosphorylation of SR15 and HNRNP proteins16 and further, to changes in AS (Fig. 1). Therefore, it is plausible to postulate that insulin resistance in obese individuals and improved insulin signaling after weight loss could modify AS. This could also create an important step gene-environment interactions if AS is regulated by both SNPs and changing insulin levels15 (Fig. 1).


Regulation of alternative splicing in obesity and weight loss.

Kaminska D, Pihlajamäki J - Adipocyte (2013)

Figure 1. Proposed mechanisms for changes in alternative splicing in obesity. Changes in phosphorylation (p in the figure) and transcription of serine/arginine-rich splicing factors (SR in the figure) may alter splicing leading to protein isoforms with different function. These effects may interact with single nucleotide polymorphisms (SNPs) in critical intron-exon boundaries. Dashed arrows refer to our own recently published data in Cell Metabolism.24
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756102&req=5

Figure 1: Figure 1. Proposed mechanisms for changes in alternative splicing in obesity. Changes in phosphorylation (p in the figure) and transcription of serine/arginine-rich splicing factors (SR in the figure) may alter splicing leading to protein isoforms with different function. These effects may interact with single nucleotide polymorphisms (SNPs) in critical intron-exon boundaries. Dashed arrows refer to our own recently published data in Cell Metabolism.24
Mentions: Although the exact pathways regulating the activity of regulatory proteins are only partially known, it is important to note that insulin signaling pathways lead to phosphorylation of SR15 and HNRNP proteins16 and further, to changes in AS (Fig. 1). Therefore, it is plausible to postulate that insulin resistance in obese individuals and improved insulin signaling after weight loss could modify AS. This could also create an important step gene-environment interactions if AS is regulated by both SNPs and changing insulin levels15 (Fig. 1).

Bottom Line: According to recent reports approximately 95-100% of human multi-exon genes undergo AS.This increases the amount of functionally different protein isoforms, and in some cases leads to metabolic diseases.Understanding of the molecular mechanisms behind the aberrantly spliced transcripts may also provide opportunities for new diagnostic approaches.

View Article: PubMed Central - PubMed

Affiliation: Institute of Public Health and Clinical Nutrition; University of Eastern Finland; Kuopio, Finland.

ABSTRACT
Alternative splicing (AS) is a mechanism by which multiple mRNA transcripts are generated from a single gene. According to recent reports approximately 95-100% of human multi-exon genes undergo AS. This increases the amount of functionally different protein isoforms, and in some cases leads to metabolic diseases. Herein we provide a brief overview of the basic aspects of splicing regulation in obesity and insulin resistance with specific examples. In addition, we review our recent findings demonstrating that weight loss regulates AS of TCF7L2 gene in both liver and adipose tissue, and that this splicing associates with changes in fatty acid and glucose metabolism. Future studies using global analysis of transcript variants and splicing regulators are needed for exploring the association of AS with metabolic alterations in obesity and type 2 diabetes (T2D). Understanding of the molecular mechanisms behind the aberrantly spliced transcripts may also provide opportunities for new diagnostic approaches.

No MeSH data available.


Related in: MedlinePlus