Loss of Tbk1 kinase activity protects mice from diet-induced metabolic dysfunction

Victoria H Cruz1, Emily N Arner1, Katherine W Wynne1

  • 1Division of Surgical Oncology, Department of Surgery and the Hamon Center for Therapeutic Oncology Research, USA.

Molecular Metabolism
|June 25, 2018
PubMed
Abstract

Insights

Loss of TANK Binding Kinase 1 (TBK1) protects against metabolic dysfunction in mice fed an obesogenic diet. This protective effect is due to TBK1 no longer inhibiting the insulin receptor.

Area of Science:

  • Biochemistry
  • Metabolic disease research
  • Molecular biology

Background:

  • TANK Binding Kinase 1 (TBK1) is implicated in metabolic regulation.
  • Amlexanox, a dual IKKε/TBK1 inhibitor, shows promise for obesity and type 2 diabetes treatment.
  • The specific metabolic role of TBK1 remains unclear due to amlexanox's dual action.

Purpose of the Study:

  • To elucidate the unique metabolic functions of TBK1.
  • To investigate the metabolic profile of mice lacking TBK1 kinase function.
  • To identify mechanisms underlying TBK1's metabolic influence.

Main Methods:

  • Examined the metabolic profile of global Tbk1 mutant mice.
  • Challenged mice with an obesogenic diet.
  • Investigated the interaction between TBK1 and the insulin receptor.

Main Results:

  • Systemic loss of TBK1 kinase function conferred a protective metabolic phenotype in mice on an obesogenic diet.
  • This protection was mediated by the absence of an inhibitory interaction between TBK1 and the insulin receptor.
  • TBK1 kinase activity negatively impacts metabolic health.

Conclusions:

  • TBK1 plays a critical role in metabolic regulation.
  • Disrupting the TBK1-insulin receptor interaction may offer therapeutic benefits for metabolic diseases.
  • Targeting TBK1 could be a strategy for treating obesity and type 2 diabetes.

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