Native adiponectin in serum binds to mammalian cells expressing T-cadherin, but not AdipoRs or calreticulin

Abstract

Adiponectin is an adipocyte-derived atypically abundant circulating factor that protects various organs and tissues through its receptors, AdipoRs, calreticulin, and T-cadherin. To identify the major binding partner of circulating native adiponectin, we expressed these receptors on the surface of HEK293 cells. Adiponectin, either that in mouse or human serum, purified from serum, or produced by mammalian cells, bound to cells expressing T-cadherin, but not to those expressing AdipoR1 or calreticulin. The stable introduction of T-cadherin and AdipoR1 into CHO cells resulted in the cell surface localization of these receptors. Native adiponectin in serum bound to cells expressing T-cadherin, not to those expressing AdipoR1. The knockdown of T-cadherin, but not AdipoRs resulted in the significant attenuation of native adiponectin binding to C2C12 myotubes. Therefore, native adiponectin binding depended on the amount of T-cadherin expressed in HEK293 cells, CHO cells, and C2C12 myotubes. Collectively, our mammalian cell-based studies suggest that T-cadherin is the major binding partner of native adiponectin in serum.

Data availability

All data were deposited in Dryad under https://dx.doi.org/10.5061/dryad.82557c0

The following data sets were generated

Article and author information

Author details

  1. Shunbun Kita

    Department of Metabolic Medicine, Osaka University, Suita, Japan
    For correspondence
    shunkita@endmet.med.osaka-u.ac.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8937-0053
  2. Shiro Fukuda

    Department of Metabolic Medicine, Osaka University, Suita, Japan
    Competing interests
    The authors declare that no competing interests exist.
  3. Norikazu Maeda

    Department of Metabolic Medicine, Osaka University, Suita, Japan
    Competing interests
    The authors declare that no competing interests exist.
  4. Iichiro Shimomura

    Department of Metabolic Medicine, Osaka University, Suita, Japan
    Competing interests
    The authors declare that no competing interests exist.

Funding

CREST

  • Shiro Fukuda
  • Iichiro Shimomura

JST

  • Shiro Fukuda
  • Iichiro Shimomura

Grant in Aid for Scientific Research (#16K09802)

  • Shunbun Kita

Grant in Aid for Scientific Research (#16K09801)

  • Norikazu Maeda

Grant in Aid for Scientific Research (#15H04853)

  • Iichiro Shimomura

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The experimental protocol was approved as No. 28-072-023 by the Ethics Review Committee for Animal Experimentation of Osaka University School of Medicine. This study also conformed to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health.

Copyright

© 2019, Kita et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,649
    views
  • 284
    downloads
  • 35
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Shunbun Kita
  2. Shiro Fukuda
  3. Norikazu Maeda
  4. Iichiro Shimomura
(2019)
Native adiponectin in serum binds to mammalian cells expressing T-cadherin, but not AdipoRs or calreticulin
eLife 8:e48675.
https://doi.org/10.7554/eLife.48675

Share this article

https://doi.org/10.7554/eLife.48675

Further reading

    1. Cell Biology
    Inês Sequeira
    Insight

    A combination of intermittent fasting and administering Wnt3a proteins to a bone injury can rejuvenate bone repair in aged mice.

    1. Cell Biology
    2. Genetics and Genomics
    Jisun So, Olivia Strobel ... Hyun Cheol Roh
    Tools and Resources

    Single-nucleus RNA sequencing (snRNA-seq), an alternative to single-cell RNA sequencing (scRNA-seq), encounters technical challenges in obtaining high-quality nuclei and RNA, persistently hindering its applications. Here, we present a robust technique for isolating nuclei across various tissue types, remarkably enhancing snRNA-seq data quality. Employing this approach, we comprehensively characterize the depot-dependent cellular dynamics of various cell types underlying mouse adipose tissue remodeling during obesity. By integrating bulk nuclear RNA-seq from adipocyte nuclei of different sizes, we identify distinct adipocyte subpopulations categorized by size and functionality. These subpopulations follow two divergent trajectories, adaptive and pathological, with their prevalence varying by depot. Specifically, we identify a key molecular feature of dysfunctional hypertrophic adipocytes, a global shutdown in gene expression, along with elevated stress and inflammatory responses. Furthermore, our differential gene expression analysis reveals distinct contributions of adipocyte subpopulations to the overall pathophysiology of adipose tissue. Our study establishes a robust snRNA-seq method, providing novel insights into the biological processes involved in adipose tissue remodeling during obesity, with broader applicability across diverse biological systems.