Program in Molecular Medicine; Davis Lab
Amino Acids, Peptides, and Proteins | Biochemical Phenomena, Metabolism, and Nutrition | Biochemistry | Cellular and Molecular Physiology | Endocrine System Diseases | Endocrinology | Genetics and Genomics | Hormones, Hormone Substitutes, and Hormone Antagonists | Lipids | Molecular Biology | Nutritional and Metabolic Diseases | Physiological Processes | Systems Biology
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.
diabetes, free fatty acids, high-fat diet, obesity, phosphoproteomics
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© 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.
DOI of Published Version
Mol Syst Biol. 2019 Aug;15(8):e8849. doi: 10.15252/msb.20198849. Link to article on publisher's site
Molecular systems biology
Dittmann A, Kennedy NJ, Soltero NL, Morshed N, Mana MD, Yilmaz OH, Davis RJ, White FM. (2019). High-fat diet in a mouse insulin-resistant model induces widespread rewiring of the phosphotyrosine signaling network. Open Access Publications by UMMS Authors. https://doi.org/10.15252/msb.20198849. Retrieved from https://escholarship.umassmed.edu/oapubs/3958
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Amino Acids, Peptides, and Proteins Commons, Biochemical Phenomena, Metabolism, and Nutrition Commons, Biochemistry Commons, Cellular and Molecular Physiology Commons, Endocrine System Diseases Commons, Endocrinology Commons, Genetics and Genomics Commons, Hormones, Hormone Substitutes, and Hormone Antagonists Commons, Lipids Commons, Molecular Biology Commons, Nutritional and Metabolic Diseases Commons, Physiological Processes Commons, Systems Biology Commons