title: Expression of the transcription factor 7-like 2 gene (TCF7L2) in human adipocytes is down regulated by insulin.
abstract: Variants in the TCF7L2 gene (transcription factor 7-like 2) have shown strong association with type 2 diabetes with two defined risk haplotypes, HapA and HapB(T2D). TCF7L2 may play a role in both glucose homeostasis and adipogenesis. Our aim was to characterize the TCF7L2 mRNA expression and regulation in human adipose tissue. We quantified TCF7L2 mRNA levels in cultured human adipocytes and in biopsies from visceral (VAT) and subcutaneous (SAT) adipose tissue from 38 obese non-diabetic subjects, using real-time PCR. The influence of haplotype and clinical traits on TCF7L2 mRNA levels were investigated. In vitro, insulin decreased TCF7L2 mRNA expression. This effect was attenuated in cells incubated with the free fatty acids palmitate or oleate. In vivo, we found significantly higher expression in SAT from more insulin resistant subjects. No correlations between TCF7L2 mRNA expression and obesity measures were observed. TCF7L2 expression was higher in VAT than in SAT and when stratifying for haplotype, this difference was seen in HapA carriers but not in non-HapA carriers. In conclusion, TCF7L2 mRNA levels in adipocytes are decreased by insulin and seem to increase in insulin resistant subjects and in HapA carriers.
authors.affiliation: Department of Clinical Sciences Malmö, Clinical Obesity, Entrance 72, Building 91, Floor 12, CRC, Lund University, Malmö University Hospital, S-205 02 Malmö, Sweden. maja.j.ahlzen@skane.se
authors.forename: Maja
authors.initials: M
authors.lastname: Ahlzén
authors.forename: Lovisa E
authors.initials: LE
authors.lastname: Johansson
authors.forename: Camilla
authors.initials: C
authors.lastname: Cervin
authors.forename: Hans
authors.initials: H
authors.lastname: Tornqvist
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.forename: Martin
authors.initials: M
authors.lastname: Ridderstråle
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D002478:Cells, Cultured; D015536:Down-Regulation; D005227:Fatty Acids / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation; D005787:Gene Frequency; D005838:Genotype; D005947:Glucose / Q000494:pharmacology; D006239:Haplotypes; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D007333:Insulin Resistance / Q000235:genetics*; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D050507:Subcutaneous Fat, Abdominal / Q000378:metabolism; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein
chemical_list: D005227:Fatty Acids; D007328:Insulin; D012333:RNA, Messenger; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D005947:Glucose