TRAIL receptor deletion in mice suppresses the inflammation of nutrient excess

Leila Idrissova1, Harmeet Malhi1, Nathan W Werneburg1

  • 1Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States.

Journal of Hepatology
|December 3, 2014
PubMed
Abstract

Insights

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor signaling drives obesity-associated inflammation and metabolic dysfunction. Blocking this pathway prevents weight gain, insulin resistance, and liver damage in mice fed a high-fat diet.

Area of Science:

  • Immunology
  • Metabolic Syndrome Research
  • Molecular Biology

Background:

  • Low-grade chronic inflammation is a hallmark of metabolic syndrome.
  • The precise mechanisms driving obesity-associated inflammation remain unclear.

Purpose of the Study:

  • To investigate the role of TRAIL receptor (TR) signaling in the development of obesity-linked inflammation.
  • To utilize genetically modified mice lacking TR to study its function in metabolic disease.

Main Methods:

  • TR knockout (TR(-/-)) and wild-type (WT) mice were fed a high-fat, high-cholesterol, high-fructose (FFC) diet or standard chow.
  • Metabolic parameters, liver injury, and inflammation in liver and adipose tissues were evaluated.
  • Macrophage chemotaxis and activation were assessed in vitro.

Main Results:

  • TR deletion completely prevented weight gain, adiposity, and insulin resistance in FFC-fed mice.
  • TR(-/-) mice showed suppressed steatohepatitis, with normal liver enzymes and reduced fat accumulation.
  • Absence of TR inhibited macrophage accumulation and activation, reducing inflammation in the liver and adipose tissue.

Conclusions:

  • Macrophage-associated inflammation in the liver and adipose tissue, driven by nutrient excess, necessitates TR signaling.
  • Targeting TR signaling may offer a therapeutic strategy for metabolic syndrome.

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