Adipocyte XBP1s regulates systemic insulin sensitivity by modulating adiponectin multimerization

  • Haibo Sha (Creator)
  • L. Yang (Creator)
  • Anping Wang (Creator)
  • Feng Liu (Creator)
  • Sander Kersten (Creator)
  • Ling Qi (Creator)

Dataset

Description

The physiological role of the spliced form of X-box-binding protein 1 (XBP1s), a key transcription factor of the endoplasmic reticulum (ER) stress response, in adipose tissue remains largely unknown. Here we show that overexpression of XBP1s promotes adiponectin multimerization in adipocytes, thereby regulating systemic glucose homeostasis. Ectopic expression of XBP1s in adipocytes improves glucose tolerance and insulin sensitivity in both lean and obese (ob/ob) mice. The beneficial effect of adipocyte XBP1s on glucose homeostasis is associated with elevated serum levels of HMW adiponectin and indeed, is adiponectin dependent. Mechanistically, XBP1s promotes adiponectin multimerization rather than activating its transcription likely through a direct regulation of the expression of several ER-chaperones involved in adiponectin maturation, including Grp78, Pdia6, ERp44 and DsbA-L. Thus, we conclude that XBP1s is an important regulator of adiponectin multimerization, which may lead to a new therapeutic approach for the treatment of type 2 diabetes and hypoadiponectinemia.
Date made available21 Nov 2013
PublisherWageningen University

Research Output

Adipocyte spliced form of X-box-binding protein 1 promotes adiponectin multimerization and systemic glucose homeostasis

Sha, H., Yang, L., Liu, M., Xia, S., Liu, Y., Liu, F., Kersten, A. H. & Qi, L., 2014, In : Diabetes. 63, 3, p. 867-879

Research output: Contribution to journalArticleAcademicpeer-review

  • 19 Citations (Scopus)

    Cite this

    Sha, H. (Creator), Yang, L. (Creator), Wang, A. (Creator), Liu, F. (Creator), Kersten, S. (Creator), Qi, L. (Creator) (21 Nov 2013). Adipocyte XBP1s regulates systemic insulin sensitivity by modulating adiponectin multimerization. Wageningen University.