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

Antje Dittmann, Norman J. Kennedy, Nina L. Soltero, Nader Morshed, Miyeko D. Mana, Ömer H. Yilmaz, Roger J. Davis, Forest M. White

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


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.

Original languageEnglish (US)
Article numbere8849
JournalMolecular Systems Biology
Issue number8
StatePublished - 2019
Externally publishedYes


  • diabetes
  • free fatty acids
  • high-fat diet
  • obesity
  • phosphoproteomics

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Information Systems
  • Applied Mathematics
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Computational Theory and Mathematics


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