en
Scientific article
English

Differential proteomic analysis of STAT6 knockout mice reveals new regulatory function in liver lipid homeostasis

Published inJournal of proteome research, vol. 8, no. 10, p. 4511-4524
Publication date2009
Abstract

Increased inflammatory signaling is a key feature of metabolic disorders. In this context, the role of increased pro-inflammatory signals has been extensively studied. By contrast, no efforts have been dedicated to study the contrasting scenario: the attenuation of anti-inflammatory signals and their role in metabolic homeostasis. IL-4 and IL-13 are anti-inflammatory cytokines signaling through the Signal Transducer and Activator of Transcription 6 (STAT6). Our study was aimed at evaluating the lack of STAT6 signaling on liver homeostasis. To this end we analyzed the liver proteome of wild type and STAT6 knock-out mice using 2D nanoscale LC-MS/MS with iTRAQ labeling technique. The coordinated changes in proteins identified by this quantitative proteome analysis indicated disturbed lipid homeostasis and a state of hepatocellular stress. Most significantly, the expression of the liver fatty acid binding protein (FABP1) was increased in the knock-out mice. In line with the elevated FABP1 expression we found latent liver lipid accumulation in the STAT6-deficient mice which was further aggravated when mice were challenged by a high fat diet. In conclusion, our study revealed a so far uncharacterized role for STAT6 in regulating liver lipid homeostasis and demonstrates the importance of anti-inflammatory signaling in the defense against the development of liver steatosis.

Keywords
  • Animals
  • Computer Simulation
  • Fatty Acid-Binding Proteins/genetics/metabolism
  • Female
  • Gene Expression
  • Heat-Shock Proteins
  • Immunohistochemistry
  • Isotope Labeling
  • Lipid Metabolism/physiology
  • Liver/metabolism
  • Male
  • Mass Spectrometry/methods
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Promoter Regions, Genetic
  • Proteome/metabolism
  • Proteomics/methods
  • STAT3 Transcription Factor/genetics/metabolism
  • STAT6 Transcription Factor/genetics/metabolism
  • Signal Transduction
  • Suppressor of Cytokine Signaling Proteins/genetics/metabolism
Citation (ISO format)
IFF, Joël et al. Differential proteomic analysis of STAT6 knockout mice reveals new regulatory function in liver lipid homeostasis. In: Journal of proteome research, 2009, vol. 8, n° 10, p. 4511–4524. doi: 10.1021/pr9003272
Main files (1)
Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal1535-3893
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4downloads

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