A disulfide-bond A oxidoreductase-like protein (DsbA-L) regulates adiponectin multimerization

Meilian Liu, Lijun Zhou, Aimin Xu, Karen S.L. Lam, Michael D. Wetzel, Ruihua Xiang, Jingjing Zhang, Xiaoban Xin, Lily Q. Dong, Feng Liu

Research output: Contribution to journalArticlepeer-review

155 Scopus citations

Abstract

Impairments in adiponectin multimerization lead to defects in adiponectin secretion and function and are associated with diabetes, yet the underlying mechanisms remain largely unknown. We have identified an adiponectin-interacting protein, previously named GST-kappa, by yeast 2-hybrid screening. The adiponectin-interacting protein contains 2 thioredoxin domains and has very little sequence similarity to other GST isoforms. However, this protein shares high sequence and secondary structure homology to bacterial disulfide-bond A oxidoreductase (DsbA) and is thus renamed DsbA-like protein (DsbA-L). DsbA-L is highly expressed in adipose tissue, and its expression level is negatively correlated with obesity in mice and humans. DsbA-L expression in 3T3-L1 adipocytes is stimulated by the insulin sensitizer rosiglitazone and inhibited by the inflammatory cytokine TNFα. Overexpression of DsbA-L promoted adiponectin multimerization while suppressing DsbA-L expression by RNAi markedly and selectively reduced adiponectin levels and secretion in 3T3-L1 adipocytes. Our results identify DsbA-L as a key regulator for adiponectin biosynthesis and uncover a potential new target for developing therapeutic drugs for the treatment of insulin resistance and its associated metabolic disorders.

Original languageEnglish (US)
Pages (from-to)18302-18307
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number47
DOIs
StatePublished - Nov 25 2008

Keywords

  • Adipose tissue
  • Insulin resistance
  • Obesity
  • Yeast 2-hybrid system

ASJC Scopus subject areas

  • General

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