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

Article Article scientifique Article Differential proteomic analysis of STAT6 knockout mice reveals new regulatory function in liver lipid homeostasis eng 2009 author Iff Joël 503151 author Wang Wei 640222 author Sajic Tatjana 647061 author Oudry Nathalie 116037 author Gueneau Estelle author Hopfgartner Gerard 0000-0002-9087-606X 31827 author Varesio Emmanuel 30230 author Szanto Ildiko 0000-0003-3566-7991 133688 4511-4524 10.1021/pr9003272 19663508 1535-3893 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. 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 Dewey 612 Dewey 615 Dewey 618.97 31 Section des sciences pharmaceutiques 17 134 Département de physiologie cellulaire et métabolisme 21C 65 Département de réadaptation et gériatrie 22B false 465 Stress oxydatif et insuline 795 Journal of proteome research 8 10 962766fa-cd5b-46bd-9b66-ed59079b3511 Article (Published version) Restricted JPR_2009_8_4511.pdf 4769665 application/pdf restrictedAccess Faculté des sciences / Section des sciences pharmaceutiques Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme Faculté de médecine / Section de médecine clinique / Département de réadaptation et gériatrie

Title	Published in	Year	Views	Downloads

Differential proteomic analysis of STAT6 knockout mice reveals new regulatory function in liver lipid homeostasis	Journal of proteome research	2009	716	5
Differential proteomic analysis of STAT6 knock-out mice reveals new regulatory function in glucose and lipid homeostasis		2007	840	733

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Iff, Joël