title: Regulation of alternative splicing in human obesity loci.
abstract: Multiple obesity susceptibility loci have been identified by genome-wide association studies, yet the mechanisms by which these loci influence obesity remain unclear. Alternative splicing could contribute to obesity by regulating the transcriptomic and proteomic diversity of genes in these loci.
  
  
  
  Based on a database search, 72 of the 136 genes at the 13 obesity loci encoded multiple protein isoforms. Thus, alternative splicing of these genes in adipose tissue samples was analyzed from the Metabolic Syndrome in Men population-based study and from two weight loss intervention studies (surgical and very low calorie diet).
  
  
  
  Alternative splicing was confirmed in 11 genes with PCR capillary electrophoresis in human subcutaneous adipose tissue. Interestingly, differential splicing of TRA2B, BAG6, and MSH5 was observed between lean individuals with normoglycemia and overweight individuals with type 2 diabetes. Of these genes, we detected fat depot-dependent splicing of TRA2B and BAG6 and weight loss-induced regulation of MSH5 splicing in the intervention studies. Finally, body mass index was a major determinant of TRA2B, BAG6, and MSH5 splicing in the combined data.
  
  
  
  This study provides evidence for alternative splicing in obesity loci, suggesting that alternative splicing at least in part mediates the obesity-associated risk in these loci.
authors: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Finland.
authors: Dorota
authors: D
authors: Kaminska
authors: Department of Surgery, University of Eastern Finland and Kuopio University Hospital, Finland.
authors: Pirjo
authors: P
authors: Käkelä
authors: Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
authors: Elina
authors: E
authors: Nikkola
authors: Department of Surgery, University of Eastern Finland and Kuopio University Hospital, Finland.
authors: Sari
authors: S
authors: Venesmaa
authors: Department of Surgery, University of Eastern Finland and Kuopio University Hospital, Finland.
authors: Imre
authors: I
authors: Ilves
authors: Institute of Biomedicine and Biocenter of Oulu, University of Oulu, Finland.|Medical Research Center Oulu & Oulu University Hospital, Finland.|Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poland.
authors: Karl-Heinz
authors: KH
authors: Herzig
authors: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Finland.
authors: Marjukka
authors: M
authors: Kolehmainen
authors: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Finland.
authors: Leila
authors: L
authors: Karhunen
authors: Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Finland.
authors: Johanna
authors: J
authors: Kuusisto
authors: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Finland.
authors: Helena
authors: H
authors: Gylling
authors: Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.|Molecular Biology Institute at UCLA, Los Angeles, California, USA.
authors: Päivi
authors: P
authors: Pajukanta
authors: Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Finland.
authors: Markku
authors: M
authors: Laakso
authors: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Finland. jussi.pihlajamaki@uef.fi.|Clinical Nutrition and Obesity Center, Kuopio University Hospital, Finland. jussi.pihlajamaki@uef.fi.
authors: Jussi
authors: J
authors: Pihlajamäki
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D017398:Alternative Splicing; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D040901:Proteomics; D011972:Receptor, Insulin / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000378:metabolism*
chemical_list: D011972:Receptor, Insulin