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Insulin resistance and adipose tissue inflammation induced by a high-fat diet are attenuated in the absence of hepcidin [preprint]

  • J.V. James
    ,
  • M. Jacob
    ,
  • Jean Christophe Deschemin
    ,
  • Nikhitha Mariya John
    ,
  • Sophie Vaulont
    ,
  • Andrew Tristan McKie
  • School of Life Sciences
    ,
  • Kings College London
    ,
  • Christian Medical College
    ,
  • Laboratory of Excellence GR-Ex
    ,
  • Institut Cochin
    ,
  • Université Paris Cité
Research Output: Other contribution Other contribution Peer-review

Open access

Sustainable Development Goals

  • SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well

Abstract

Increased body iron stores and inflammation in adipose tissue have been implicated in the pathogenesis of insulin resistance (IR) and type 2 diabetes mellitus. However, the underlying basis of these associations are unclear. In order to assess this, we studied how IR and associated inflammation in adipose tissue developed in the presence of increased body iron stores. Male hepcidin knock-out (Hamp1-/-) mice, which have increased body iron stores, and wild-type (WT) mice were fed a high-fat diet (HFD) for 12 and 24 weeks. Development of IR and metabolic parameters linked to this, insulin signaling in tissue, and inflammation and iron-related parameters in visceral adipose tissue were studied in these animals. HFD-feeding resulted in impaired glucose tolerance in both genotypes of mice. In response to the HFD for 24 weeks, Hamp1-/- mice gained less body weight and developed less IR than corresponding WT mice. This was associated with less lipid accumulation in the liver and decreased inflammation and lipolysis in the adipose tissue in the knock-out mice, than in the WT animals. Fewer macrophages infiltrated the adipose tissue in the knockout mice than in wild-type mice, with these macrophages exhibiting a predominantly anti-inflammatory (M2-like) phenotype. These observations suggest a novel role of hepcidin (central regulator of systemic iron homeostasis) in the development of inflammation in adipose tissue and insulin resistance, in response to a high-fat diet.

Publication Information

Output type

Research Output: Other contribution Other contribution Peer-review

Original language

Undefined/Unknown

Publication milestones

  • Accepted/In press - 15/09/2021
  • Published - 2021

Publication status

Published - 2021

Publisher

biorxiv

Publication IDs

  • ORCID: /0000-0002-3494-1808/work/109033589
  • Scopus: 85118270189

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