Low expression of the GILZ may contribute to adipose inflammation and altered adipokine production in human obesity

Mi Jeong Lee, Rong Ze Yang, Kalypso Karastergiou, Steven R. Smith, Jeffery R. Chang, Da Wei Gong, Susan K. Fried

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The glucocorticoid-induced leucine zipper (GILZ), a primary target of glucocorticoids, is expressed in human adipocytes, but its importance in adipocyte function is unknown. Because TNFα is increased in obese adipose tissue and antagonizes a number of glucocorticoid actions, we investigated the interplay of these pathways. GILZ knockdown increased and GILZ overexpression decreased interleukin-6 (IL-6) and leptin mRNA and protein secretion. GILZ knockdown increased the magnitude of the glucocorticoid effect on leptin secretion, but did not affect the glucocorticoid suppression of IL-6. Although GILZ silencing decreased adiponectin mRNA levels, it did not affect the amount of adiponectin secreted. GILZ negatively modulated pro-inflammatory signaling pathways, blocking basal and TNFα-stimulated (1 h) p65 nuclear factor κB nuclear translocation and transcriptional activity by binding to p65 in the cytoplasm. GILZ silencing increased basal ERK1/2 and JNK phosphorylation, and decreased MAPK phosphatase-1 protein levels. Longer term TNFα (4 h or 24 h) treatment decreased GILZ expression in human adipocytes. Furthermore, adipose tissue GILZ mRNA levels were reduced in proportion to the degree of obesity and expression of inflammatory markers. Overall, these results suggest that GILZ antagonizes the proinflammatory effects of TNFα in human adipocytes, and its downregulation in obesity may contribute to adipose inflammation and dysregulated adipokine production, and thereby systemic metabolism.

Original languageEnglish
Pages (from-to)1256-1263
Number of pages8
JournalJournal of Lipid Research
Volume57
Issue number7
DOIs
StatePublished - Jul 2016
Externally publishedYes

Keywords

  • Glucocorticoid-induced leucine zipper
  • Interleukin-6
  • Leptin
  • Mitogen-activated protein kinase
  • Mitogen-activated protein kinase phosphatase-1
  • Nuclear factor κB

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