PID1 in adipocytes modulates whole-body glucose homeostasis

• Published in: Biochimica et biophysica acta. Gene regulatory mechanisms 2018-02, Vol.1861 (2), p.125-132
• Main Authors: Chen, Ling, Wang, Xing-Yun, Zhu, Jin-Gai, You, Liang-Hui, Wang, Xing, Cui, Xian-Wei, Shi, Chun-Mei, Huang, Fang-Yan, Zhou, Ya-Hui, Yang, Lei, Pang, Ling-Xia, Gao, Yao, Ji, Chen-Bo, Guo, Xi-Rong
• Format: Article
• Language: English
• Subjects: 3T3-L1 Cells; Adipocytes - metabolism; Adipose Tissue, White - metabolism; Animals; Carrier Proteins - genetics; Carrier Proteins - metabolism; Fatty Acid-Binding Proteins - genetics; Fatty Acid-Binding Proteins - metabolism; Glucose - metabolism; Glucose Transporter Type 4 - metabolism; GLUT4; Homeostasis; Humans; Insulin - metabolism; Insulin Resistance; LRP1; Mice; Mice, Knockout; Mice, Transgenic; Phosphatidylinositol 3-Kinases - metabolism; PID1; Protein Binding; Receptors, LDL - metabolism; Tumor Suppressor Proteins - metabolism
• ISSN: 1874-9399; 1876-4320
• DOI: 10.1016/j.bbagrm.2018.01.001

The novel obesity-associated protein Phosphotyrosine Interaction Domain containing 1 (PID1) inhibits insulin-PI3K/Akt signaling pathway and insulin-stimulated glucose uptake in vitro. In this study, we generated fat tissue-specific aP2-PID1 transgenic (aP2-PID1tg) mice and PID1 knockout (PID1−/−) mice to explore how PID1 affects glucose metabolism in vivo. We observed insulin resistance and impaired insulin-PI3K/Akt signaling in aP2-PID1tg mice. Consistent with these data, the PID1−/− mice displayed improved glucose tolerance and insulin sensitivity under chow diet, with increased Akt phosphorylation in white adipose tissue (WAT). We further demonstrated that PID1 could interact with low density lipoprotein receptor-related protein 1 (LRP1) but not the insulin receptor (IR) in adipocytes, and its overexpression could lead to decreased GLUT4 level. Our results thus indentify PID1 as a critical regulator of glucose metabolism in adipocytes. •The aP2-PID1tg mice showed glucose intolerance and impaired insulin-PI3K/Akt signaling.•PID1-/- mice displayed improved insulin sensitivity and increased Akt phosphorylation in white adipose tissue.•PID1 interacts with LRP1; PID1 overexpression is associated with decreased GLUT4 protein level.•PID1 inhibited glucose uptake of human adipocytes.•A large dataset shows that PID1 mRNA is highly expressed in adipose tissue from obese patients.