Human T2D-Associated Gene IMP2/IGF2BP2 Promotes the Commitment of Mesenchymal Stem Cells Into Adipogenic Lineage

Abstract

Excessive adiposity is the main cause of obesity and type two diabetes (T2D). Variants in human IMP2/IGF2BP2 gene are associated with increased risk of T2D. However, little is known about its role in adipogenesis and in insulin resistance. Here, we investigate the function of IMP2 during adipocyte development. Mice with Imp2 deletion in mesenchymal stem cells (MSC) are resistant to diet-induced obesity without glucose and insulin tolerance affected. Imp2 is essential for the early commitment of adipocyte-derived stem cells (ADSC) into preadipocytes, but the deletion of Imp2 in MSC is not required for the proliferation and terminal differentiation of committed preadipocytes. Mechanistically, Imp2 binds Wnt receptor Fzd8 mRNA and promotes its degradation by recruiting CCR4-NOT deadenylase complex in an mTOR-dependent manner. Our data demonstrate that Imp2 is required for maintaining white adipose tissue homeostasis through controlling mRNA stability in ADSC. However, the contribution of IMP2 to insulin resistance, a main risk of T2D, is not evident.