Targeted proteomics reveals strain‐specific changes in the mouse insulin and central metabolic pathways after a sustained high‐fat diet. Issue 1 (16th July 2013)

• Record Type: Journal Article
• Authors: Sabidó, Eduard; Wu, Yibo; Bautista, Lucia; Porstmann, Thomas; Chang, Ching‐Yun; Vitek, Olga; Stoffel, Markus; Aebersold, Ruedi
• Is Part Of: Molecular systems biology. Volume 9:Issue 1(2013)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2013-07-16
• Subjects: liver -- metabolic syndrome -- NAFLD -- proteomics -- SRM; Molecular biology -- Periodicals; Systems biology -- Periodicals; 572.8
• DOI: 10.1038/msb.2013.36
• Languages: English
• ISSNs: 1744-4292

Abstract

Abstract : The metabolic syndrome is a collection of risk factors including obesity, insulin resistance and hepatic steatosis, which occur together and increase the risk of diseases such as diabetes, cardiovascular disease and cancer. In spite of intense research, the complex etiology of insulin resistance and its association with the accumulation of triacylglycerides in the liver and with hepatic steatosis remains not completely understood. Here, we performed quantitative measurements of 144 proteins involved in the insulin‐signaling pathway and central metabolism in liver homogenates of two genetically well‐defined mouse strains C57BL/6J and 129Sv that were subjected to a sustained high‐fat diet. We used targeted mass spectrometry by selected reaction monitoring (SRM) to generate accurate and reproducible quantitation of the targeted proteins across 36 different samples (12 conditions and 3 biological replicates), generating one of the largest quantitative targeted proteomics data sets in mammalian tissues. Our results revealed rapid response to high‐fat diet that diverged early in the feeding regimen, and evidenced a response to high‐fat diet dominated by the activation of peroxisomal β‐oxidation in C57BL/6J and by lipogenesis in 129Sv mice. Abstract : Quantitative measurement of proteins involved in insulin signaling and central metabolism in C57BL/6J and 129Sv mice subjected to a sustained high‐fat diet reveals that the two strains diverge early in their response to the feeding regimen. Synopsis: Quantitative measurement of proteins involved in insulin signaling and central metabolism in C57BL/6J and 129Sv mice subjected to a sustained high‐fat diet reveals that the two strains diverge early in their response to the feeding regimen. Quantitative targeted protein measurements were designed to quantify murine proteins covering the insulin‐signaling pathwayand the lipid and carbohydrate metabolism and used to compare the differential effect of a persistent high‐fat diet in C57BL/6Jand 129Sv mouse strains. Differential effect of a persistent high‐fat diet were compared in C57BL/6J and 129Sv mouse strains. Differences in protein abundances suggest that peroxisomal β‐oxidation is actively promoted in fatty C57BL/6J mice whereaslipogenesis activation dominates the response of 129Sv mice. Most strain‐specific changes were apparent early in the regimen when phenotypic changes were already set, but not yet verypronounced and they allow a clear discrimination of the mouse strains at an early stage during the long‐term high‐fat diet. Persistent high‐fat diet also alters the transient changes that normally occur in C57BL/6J and 129Sv mice in response to fastingor food intake.