Adipocyte-specific deficiency of Nfe2l1 disrupts plasticity of white adipose tissues and metabolic homeostasis in mice

Biochem Biophys Res Commun. 2018 Sep 3;503(1):264-270. doi: 10.1016/j.bbrc.2018.06.013. Epub 2018 Jun 25.

Abstract

The maintenance of healthy adipose tissues is essential for efficient regulation of energy homeostasis. Nuclear factor-erythroid 2-related factor 1 (NFE2L1, also known as Nrf1), a CNC-bZIP protein, is a master regulator of the cellular adaptive response to stresses. To investigate the role of NFE2L1 in adipocytes, we bred a line of mice with adipocyte-specific Nfe2l1 knockout (Nfe2l1(f)-KO), and found that Nfe2l1(f)-KO mice exhibited a dramatically reduced subcutaneous adipose tissue (SAT) mass, insulin resistance, adipocyte hypertrophy, and severe adipose inflammation. Mechanistic studies revealed that Nfe2l1 deficiency may disturb the expression of lipolytic genes in adipocytes, leading to adipocyte hypertrophy followed by inflammation, pyroptosis, and insulin resistance. Our findings reveal a novel role for NFE2L1 in regulating adipose tissue plasticity and energy homeostasis.

Keywords: Adipose; Inflammation; Lipolysis; NFE2L1; Pyroptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism
  • Adipocytes / pathology*
  • Adipose Tissue, White / cytology
  • Adipose Tissue, White / metabolism
  • Adipose Tissue, White / pathology*
  • Adiposity
  • Animals
  • Body Fat Distribution
  • Energy Metabolism
  • Gene Expression Regulation
  • Hypertrophy
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / pathology*
  • Insulin Resistance
  • Lipolysis*
  • Male
  • Mice
  • Mice, Knockout
  • NF-E2-Related Factor 1 / genetics*

Substances

  • NF-E2-Related Factor 1
  • Nfe2L1 protein, mouse