High-fat diet in a mouse insulin-resistant model induces widespread rewiring of the phosphotyrosine signaling network.
Antje DittmannNorman J KennedyNina L SolteroNader MorshedMiyeko D ManaÖmer H YilmazRoger J DavisForest M WhitePublished in: Molecular systems biology (2020)
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.
Keyphrases
- high fat diet
- insulin resistance
- type diabetes
- adipose tissue
- fatty acid
- high fat diet induced
- health risk
- reactive oxygen species
- metabolic syndrome
- glycemic control
- skeletal muscle
- electronic health record
- induced apoptosis
- heavy metals
- tyrosine kinase
- protein kinase
- single molecule
- drinking water
- big data
- single cell
- cell death
- oxidative stress
- body mass index
- cancer therapy
- combination therapy
- artificial intelligence
- induced pluripotent stem cells
- drug delivery
- deep learning
- data analysis