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Title

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

Authors
Gueneau, Estelle
Szanto, Ildiko
Published in Journal of Proteome Research. 2009, vol. 8, no. 10, p. 4511-24
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 AnimalsComputer SimulationFatty Acid-Binding Proteins/genetics/metabolismFemaleGene ExpressionHeat-Shock ProteinsImmunohistochemistryIsotope LabelingLipid Metabolism/physiologyLiver/metabolismMaleMass Spectrometry/methodsMiceMice, Inbred BALB CMice, KnockoutPromoter Regions, GeneticProteome/metabolismProteomics/methodsSTAT3 Transcription Factor/genetics/metabolismSTAT6 Transcription Factor/genetics/metabolismSignal TransductionSuppressor of Cytokine Signaling Proteins/genetics/metabolism
Identifiers
PMID: 19663508
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Article (Published version) (4.5 MB) - document accessible for UNIGE members only Limited access to UNIGE
Other version: http://pubs.acs.org/doi/pdfplus/10.1021/pr9003272
Structures
Research group Stress oxydatif et insuline (795)
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(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. 4511-24. https://archive-ouverte.unige.ch/unige:5148

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Deposited on : 2010-02-09

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