Histidine PhosPhorylation and Obesity Protein histidine phosphorylation is a poorly characterized post-translational modification. Its importance in mammalian cellular function is emerging from the discovery of histidine kinases and phosphatases and their substrates. Recently, histidine phosphorylation has been involved in heart failure and cancer. Obesity and type 2 diabetes remain challenging disorders due to growing prevalence around the world and poorly efficient treatments. Regarding metabolic disorders, histidine phosphorylation state has been associated with insulin secretion regulation in pancreas. However, the role of histidine phosphorylation in insulin sensitivity in liver, skeletal muscle or adipose tissue and/or in obesity is still not known. The main aim of the present project is to determine whether protein histidine phosphorylation plays a role in obesity-associated metabolic dysfunction. Thus, we will determine if obesity modify global histidine phosphorylation level, histidine kinases and phosphatases expression or activity, and specific protein histidine phosphorylation. Then, we will evaluate whether a change of histidine phosphorylation level can impact whole-body glucose metabolism and body weight/composition by using transgenic mice deficient in histidine phosphatases and/or kinases.
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