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  • High-fat diet in a mouse insulin-resistant model induces widespread rewiring of the phosphotyrosine signaling network.

High-fat diet in a mouse insulin-resistant model induces widespread rewiring of the phosphotyrosine signaling network.

Molecular systems biology (2019-08-30)
Antje Dittmann, Norman J Kennedy, Nina L Soltero, Nader Morshed, Miyeko D Mana, Ömer H Yilmaz, Roger J Davis, Forest M White
ABSTRACT

Obesity-associated type 2 diabetes and accompanying diseases have developed into a leading human health risk across industrialized and developing countries. The complex molecular underpinnings of how lipid overload and lipid metabolites lead to the deregulation of metabolic processes are incompletely understood. We assessed hepatic post-translational alterations in response to treatment of cells with saturated and unsaturated free fatty acids and the consumption of a high-fat diet by mice. These data revealed widespread tyrosine phosphorylation changes affecting a large number of enzymes involved in metabolic processes as well as canonical receptor-mediated signal transduction networks. Targeting two of the most prominently affected molecular features in our data, SRC-family kinase activity and elevated reactive oxygen species, significantly abrogated the effects of saturated fat exposure in vitro and high-fat diet in vivo. In summary, we present a comprehensive view of diet-induced alterations of tyrosine signaling networks, including proteins involved in fundamental metabolic pathways.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
O-Phospho-L-tyrosine
Sigma-Aldrich
Palmitic acid, BioXtra, ≥99%
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Monoclonal Anti-Phosphotyrosine antibody produced in mouse, clone PT-66, ascites fluid
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DL-Dithiothreitol, ≥99.0% (RT)
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Anti-Phosphotyrosine Antibody, clone 4G10®, clone 4G10®, Upstate®, from mouse
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Dasatinib
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Protein G Plus-Agarose Suspension, Protein G PLUS agarose suspension specifically formulated for immunoprecipitation.
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Fluorometric Intracellular Ros Kit, sufficient for 200 fluorometric tests (red)
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Acetic acid, glacial, ≥99.99% trace metals basis
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Fluorometric Intracellular Ros Kit, sufficient for 200 fluorometric tests (green)
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Trizma® base, Primary Standard and Buffer, ≥99.9% (titration), crystalline
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Sodium hydroxide solution, 1.0 N, BioReagent, suitable for cell culture
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Sodium phosphate monobasic, BioReagent, for molecular biology, anhydrous, ≥98%
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Urea, ACS reagent, 99.0-100.5%
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Oleic acid, BioReagent, suitable for cell culture
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Triethylammonium bicarbonate buffer, 1.0 M, pH 8.5±0.1
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Iodoacetamide, BioUltra
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Acetonitrile, HPLC Plus, ≥99.9%