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

Gueneau, Estelle
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
PMID: 19663508
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Research group Stress oxydatif et insuline (795)
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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. doi: 10.1021/pr9003272 https://archive-ouverte.unige.ch/unige:5148

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Deposited on : 2010-02-09

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