The role of transcription factor 7-like 2 in metabolic disorders

Transcription factor 7-like 2 (TCF7L2), a member of the T cell factor/lymphoid enhancer factor family, generally forms a complex with β-catenin to regulate the downstream target genes as an effector of the canonical Wnt signalling pathway. TCF7L2 plays a vital role in various biological processes and functions in many organs and tissues, including the liver, islet and adipose tissues. Further, TCF7L2 down-regulates hepatic gluconeogenesis and promotes lipid accumulation. In islets, TCF7L2 not only affects the insulin secretion of the β-cells but also has an impact on other cells. In addition, TCF7L2 influences adipogenesis in adipose tissues. Thus, an out-of-control TCF7L2 expression can result in metabolic disorders. The TCF7L2 gene is composed of 17 exons, generating 13 different transcripts, and has many single-nucleotide polymorphisms (SNPs). The discovery that these SNPs have an impact on the risk of type 2 diabetes (T2D) has attracted thorough investigations in the study of TCF7L2. Apart from T2D, TCF7L2 SNPs are also associated with type 1, posttransplant and other types of diabetes. Furthermore, TCF7L2 variants affect the progression of other disorders, such as obesity, cancers, metabolic syndrome and heart diseases. Finally, the interaction between TCF7L2 variants and diet also needs to be investigated.