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

Haibo Sha, Liu Yang, Meilian Liu, Sheng Xia, Yong Liu, Feng Liu, Sander Kersten, Ling Qi

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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. In this study, 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 highmolecular- weight 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 glucose-regulated protein 78 kDa, protein disulfide isomerase family A, member 6, ER protein 44, and disulfide bond oxidoreductase A-like protein. 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.

Original languageEnglish (US)
Pages (from-to)867-879
Number of pages13
JournalDiabetes
Volume63
Issue number3
DOIs
StatePublished - Mar 1 2014

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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