A macrophage NBR1-MEKK3 complex triggers JNK-mediated adipose tissue inflammation in obesity Academic Article uri icon

Overview

MeSH Major

  • Adipose Tissue
  • Inflammation
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinase 3
  • Obesity
  • Proteins

abstract

  • The c-Jun NH(2)-terminal kinase (JNK) is a critical determinant of obesity-associated inflammation and glucose intolerance. The upstream mechanisms controlling this pathway are still unknown. Here we report that the levels of the PB1 domain-containing adaptor NBR1 correlated with the expression of proinflammatory molecules in adipose tissue from human patients with metabolic syndrome, suggesting that NBR1 plays a key role in adipose-tissue inflammation. We also show that NBR1 inactivation in the myeloid compartment impairs the function, M1 polarization, and chemotactic activity of macrophages; prevents inflammation of adipose tissue; and improves glucose tolerance in obese mice. Furthermore, we demonstrate that an interaction between the PB1 domains of NBR1 and the mitogen-activated kinase kinase 3 (MEKK3) enables the formation of a signaling complex required for the activation of JNK. Together, these discoveries identify an NBR1-MEKK3 complex as a key regulator of JNK signaling and adipose tissue inflammation in obesity.

publication date

  • September 2, 2014

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4156534

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2014.06.008

PubMed ID

  • 25043814

Additional Document Info

start page

  • 499

end page

  • 511

volume

  • 20

number

  • 3