High-fat diet in a mouse insulin-resistant model induces widespread rewiring of the phosphotyrosine signaling network
Kennedy, Norman J.
Soltero, Nina L.
Mana, Miyeko D.
Yilmaz, Omer H.
Davis, Roger J.
White, Forest M.
Document TypeJournal Article
free fatty acids
Amino Acids, Peptides, and Proteins
Biochemical Phenomena, Metabolism, and Nutrition
Cellular and Molecular Physiology
Endocrine System Diseases
Genetics and Genomics
Hormones, Hormone Substitutes, and Hormone Antagonists
Nutritional and Metabolic Diseases
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AbstractObesity-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.
Mol Syst Biol. 2019 Aug;15(8):e8849. doi: 10.15252/msb.20198849. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/41170
Rights© 2019 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as © 2019 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.