Abstract
BackgroundA peptidyl prolyl cis/trans isomerase, Pin1, regulates insulin signal transduction. Pin1 reduces responses to insulin stimulation by binding CRTC2 (CREB-regulated transcriptional co-activator 2) and PPARγ (peroxisome prolifereator- activated receptor γ), but conversely enhances insulin signaling by binding IRS-1 (insulin receptor substrate-1), Akt kinase, and Smad3. Therefore, it is still unclear whether Pin1 inhibits or enhances adipose cell differentiation.Methodology/Principal FindingsPin1−/− and wild-type mice were fed with high fat diets and adipose tissue weight was measured. Compared to wild-type mice, Pin1−/− mice had lower adipose tissue weight, while the weight of other tissues was similar. Mouse embryo fibroblasts (MEFs), prepared from both groups of mice, were induced to differentiate into adipose cells by stimulation with insulin. However, the rate of differentiation of MEFs from Pin1−/− mice was less than that of MEFs from wild-type mice. The rate of insulin-induced MEF cell differentiation in Pin1−/− mice was restored by increasing expression of Pin1. We found that Pin1 binds to phosphoThr172- and phosphoSer271-Pro sites in CREB suppress the activity in COS-7 cells.Conclusion and SignificancePin1 enhanced the uptake of triglycerides and the differentiation of MEF cells into adipose cells in response to insulin stimulation. Results of this study suggest that Pin1 down-regulation could be a potential approach in obesity-related dysfunctions, such as high blood pressure, diabetes, non-alcoholic steatohepatitis.
Highlights
A peptidyl prolyl cis/trans isomerase, Pin1, binds to phosphorylated Ser/Thr-Pro motifs in a variety of proteins and catalyzes cis/trans isomerization of peptidyl prolyl bonds
We found that Pin1 binds to phosphoThr172- and phosphoSer271-Pro sites in CREB suppress the activity in COS-7 cells
Pin1 enhanced the uptake of triglycerides and the differentiation of Mouse embryo fibroblasts (MEFs) cells into adipose cells in response to insulin stimulation
Summary
A peptidyl prolyl cis/trans isomerase, Pin, binds to phosphorylated Ser/Thr-Pro motifs in a variety of proteins and catalyzes cis/trans isomerization of peptidyl prolyl bonds. Pin binds phosphorylated Ser84-Pro of PPARc to reduce its transcriptional activity [3]. Pin binds phosphorylated Ser434-Pro of IRS1 to directly upregulate insulin signal transduction [5]. Pin reduces responses to insulin stimulation by binding CRTC2 (CREB-regulated transcriptional co-activator 2) and PPARc (peroxisome prolifereatoractivated receptor c), but enhances insulin signaling by binding IRS-1 (insulin receptor substrate-1), Akt kinase, and Smad. Pin reduces responses to insulin stimulation by binding CRTC2 (CREB-regulated transcriptional co-activator 2) and PPARc (peroxisome prolifereatoractivated receptor c), but enhances insulin signaling by binding IRS-1 (insulin receptor substrate-1), Akt kinase, and Smad3 It is still unclear whether Pin inhibits or enhances adipose cell differentiation
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
