TCF7L2, short for Transcription factor 7 like 2, is a transcription factor and a key transcriptional effector of the Wnt/β-catenin signaling pathway, regulating gene expression. It was initially identified in cancer and embryologic developmental studies, and later linked to type 2 diabetes (T2D), indicating its role in metabolic disorders and homeostasis [1].

In transgenic mouse in vivo studies, TCF7L2 has been shown to play important roles in adipose tissue biology and systemic metabolism. For example, TCF7L2 knockdown in abdominal adipose progenitor cells (APCs) led to dose-dependent activation of WNT/β-catenin signaling, impaired proliferation, and dose-dependent effects on adipogenesis, while over-expression of TCF7L2 accelerated adipogenesis. The T2D-risk allele at rs7903146 was associated with reduced APC TCF7L2 expression and enhanced adipose tissue insulin sensitivity [2].

In conclusion, TCF7L2 plays a crucial role in multiple biological processes. Its functions in adipose tissue biology and systemic metabolism, as revealed through mouse models, contribute to our understanding of its role in T2D. The gene's association with T2D, along with its complex role in adipose progenitor biology, provides insights into the genetic susceptibility to T2D and potentially other related metabolic disorders.