TBK1 at the Crossroads of Inflammation and Energy Homeostasis in Adipose Tissue

Peng Zhao, Kai in Wong, Xiaoli Sun, Shannon M. Reilly, Maeran Uhm, Zhongji Liao, Yuliya Skorobogatko, Alan R. Saltiel

Research output: Contribution to journalArticlepeer-review

142 Scopus citations

Abstract

The noncanonical IKK family member TANK-binding kinase 1 (TBK1) is activated by pro-inflammatory cytokines, but its role in controlling metabolism remains unclear. Here, we report that the kinase uniquely controls energy metabolism. Tbk1 expression is increased in adipocytes of HFD-fed mice. Adipocyte-specific TBK1 knockout (ATKO) attenuates HFD-induced obesity by increasing energy expenditure; further studies show that TBK1 directly inhibits AMPK to repress respiration and increase energy storage. Conversely, activation of AMPK under catabolic conditions can increase TBK1 activity through phosphorylation, mediated by AMPK's downstream target ULK1. Surprisingly, ATKO also exaggerates adipose tissue inflammation and insulin resistance. TBK1 suppresses inflammation by phosphorylating and inducing the degradation of the IKK kinase NIK, thus attenuating NF-κB activity. Moreover, TBK1 mediates the negative impact of AMPK activity on NF-κB activation. These data implicate a unique role for TBK1 in mediating bidirectional crosstalk between energy sensing and inflammatory signaling pathways in both over- and undernutrition. Adipose tissue inflammation plays an important role in reducing energy expenditure in obesity.

Original languageEnglish (US)
Pages (from-to)731-743.e12
JournalCell
Volume172
Issue number4
DOIs
StatePublished - Feb 8 2018
Externally publishedYes

Keywords

  • AMPK
  • cytokine
  • energy expenditure
  • insulin resistance
  • mitochondria
  • NFκB
  • obesity
  • protein phosphorylation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint

Dive into the research topics of 'TBK1 at the Crossroads of Inflammation and Energy Homeostasis in Adipose Tissue'. Together they form a unique fingerprint.

Cite this