The role of FoxK1 in insulin signaling and adipose tissue metabolism

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Insulin is a central hormone in the regulation of nutrient and energy homeostasis. In the wake of the alarming worldwide increase in type-2 diabetes and obesity, a major focus of research is understanding the mechanisms underlying the insulin resistance characteristic of these metabolic disorders. Members of the forkhead box (FOX) transcription factor family FOXO and FOXA2, have been shown to play a role in insulin metabolic actions. Data obtained by the hosting group demonstrate that another FOX protein, FOXK1, not previously linked to insulin action, may also play a role in this process. Interestingly, opposite of FOXO proteins, FOXK1 undergoes translocation into the nucleus in response to insulin stimulation. In this project, we propose the study of FOXK1 as a novel factor mediating insulin responses in adipocytes. By using comprehensive in vitro and in vivo studies this project will characterize the signaling events leading to FOXK1 activation, its phosphorylation sites, binding partners and target genes. In addition, mice with an adipocyte-specific deletion of FOXK1 will be generated for the study of the physiological function of this factor in white and brown adipose tissues, as well as its potential involvement in pathological conditions such as obesity and insulin resistance.