UMMS Affiliation

Program in Molecular Medicine; Davis Lab

Publication Date


Document Type



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

Journal/Book/Conference Title

Molecular systems biology

Related Resources

Link to Article in PubMed

PubMed ID


Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.