CL316243 treatment mitigates the inflammation in white adipose tissues of juvenile adipocyte-specific Nfe2l1 knockout mice

Zhendi Wang, Yongyong Hou, Suping Ren, Zhiyuan Liu, Zhuo Zuo, Sicui Huang, Wanqi Wang, Huihui Wang, Yanyan Chen, Yuanyuan Xu, Masayuki Yamamoto, Qiang Zhang, Jingqi Fu, Jingbo Pi

Research output: Contribution to journalArticlepeer-review

Abstract

Nuclear factor-erythroid 2-related factor 1 (NFE2L1) is a key transcription factor that regulates cellular adaptive responses to various stresses. Our previous studies revealed that adult adipocyte-specific Nfe2l1-knockout [Nfe2l1(f)-KO] mice show adipocyte hypertrophy and severe adipose inflammation, which can be worsened by rosiglitazone, a peroxisome proliferator-activated receptor γ agonist. To further assess the crucial roles of NFE2L1 in adipocytes, we investigated the effect of CL316243, a β3 adrenergic agonist that promotes lipolysis via a post-translational mechanism, on adipose inflammation in juvenile Nfe2l1(f)-KO mice. In contrast to adult mice, 4-week-old juvenile Nfe2l1(f)-KO mice displayed a normal fat distribution but reduced fasting plasma glycerol levels and elevated adipocyte hypertrophy and macrophage infiltration in inguinal and gonadal WAT. In addition, Nfe2l1(f)-KO mice had decreased expression of multiple lipolytic genes and reduced lipolytic activity in WAT. While 7 days of CL316243 treatment showed no significant effect on adipose inflammation in Nfe2l1-Floxed control mice, the same treatment dramatically alleviated macrophage infiltration and mRNA expression of inflammation and pyroptosis-related genes in WAT of Nfe2l1(f)-KO mice. Together with previous findings in adult mice, the current study highlights that NFE2L1 plays a fundamental regulatory role in lipolytic gene expression and thus might be an important target to improve adipose plasticity and lipid homeostasis.

Original languageEnglish
Pages (from-to)289-298
Number of pages10
JournalFree Radical Biology and Medicine
Volume165
DOIs
Publication statusPublished - 2021 Mar
Externally publishedYes

Keywords

  • Adipose
  • CL316243
  • Inflammation
  • Lipolysis
  • NFE2L1

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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