A feedback control of insulin signaling by transcription factor HMG box‐containing protein 1 (HBP1) in adipocytes

Abstract

Adipocytes are sensitive to insulin control of cellular glucose utilization, thereby facilitating the maintenance of blood glucose concentration. Previously we demonstrated that transcription factor HBP1 is highly expressed in differentiated adipocytes, which, together with CCAAT/enhancer‐binding proteins C/EBPβ and C/EBPα, regulates adipocyte differentiation. To further gain insight into the biological role of HBP1 in mature adipocytes, here, we employed mouse embryonic fibroblast (MEF)‐derived adipocytes to test the hypothesis that HBP1 might regulate insulin sensitivity in adipocytes. First, suppression of HBP1 by siRNA‐mediated gene silencing significantly attenuated glucose uptake as shown by 2‐NBDG glucose uptake assay. We then examined the insulin‐signaling pathway to unravel the molecular mechanism by which HBP1 commands adipocytes to take up glucose. Under serum starvation, the transcription of insulin receptor (InR) was increased, whereas HBP1 silencing down‐regulated the expression of InR in adipocytes, indicating that HBP1 is able to promote insulin sensitivity under insulin insufficient state. However, the addition of insulin (2 nM for 6 h) led to a significant decrease in the transcription of HBP1, InR, and IRS1/2 (insulin receptor substrate 1/2). Moreover, HBP1 siRNA led to increased level of p‐S307 IRS‐1 that is associated with blockade of the insulin signaling, and also resulted in an unexpected induction of glucose transporter 4 (GLUT4). The upregulation of GLUT4 may function as a compensation mechanism for the defective insulin signaling caused by HBP1 silencing. Taken as a whole, our results reveal a key feedback control mechanism for HBP1 in regulating insulin signaling and glucose metabolism.Support or Funding InformationThis work was supported by the grant to MOST 105‐2320‐B‐039‐044‐MY2 C‐Y Huang.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.