Adipocyte iron levels impinge on a fat-gut crosstalk to regulate intestinal lipid absorption and mediate protection from obesity

Zhuzhen Zhang, Jan Bernd Funcke, Zhenzhen Zi, Shangang Zhao, Leon G. Straub, Yi Zhu, Qingzhang Zhu, Clair Crewe, Yu A. An, Shiuhwei Chen, Na Li, May yun Wang, Alexandra L. Ghaben, Charlotte Lee, Laurent Gautron, Luke J. Engelking, Prithvi Raj, Yingfeng Deng, Ruth Gordillo, Christine M. KusminskiPhilipp E. Scherer

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Iron overload is positively associated with diabetes risk. However, the role of iron in adipose tissue remains incompletely understood. Here, we report that transferrin-receptor-1-mediated iron uptake is differentially required for distinct subtypes of adipocytes. Notably, adipocyte-specific transferrin receptor 1 deficiency substantially protects mice from high-fat-diet-induced metabolic disorders. Mechanistically, low cellular iron levels have a positive impact on the health of the white adipose tissue and can restrict lipid absorption from the intestine through modulation of vesicular transport in enterocytes following high-fat diet feeding. Specific reduction of adipocyte iron by AAV-mediated overexpression of the iron exporter Ferroportin1 in adult mice effectively mimics these protective effects. In summary, our studies highlight an important role of adipocyte iron in the maintenance of systemic metabolism through an adipocyte-enterocyte axis, offering an additional level of control over caloric influx into the system after feeding by regulating intestinal lipid absorption.

Original languageEnglish (US)
Pages (from-to)1624-1639.e9
JournalCell Metabolism
Volume33
Issue number8
DOIs
StatePublished - Aug 3 2021

Keywords

  • Fpn1
  • adipocyte
  • diabetes and obesity
  • enterocyte
  • intestine
  • iron
  • lipid absorption
  • transferrin receptor 1
  • vesicular transport
  • white adipose tissue

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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