Systems biology strategies in studies of energy homeostasis in vivo

In this chapter the authors report on their experience with the analysis and modeling of data obtained from studies of animal models related to obesity and metabolic syndrome. The complex interactions of genetic and environmental factors contributing to the failure of energy balance that lead to obesity, as well as tight systemic regulation to maintain energy homeostasis, require application of the systems biology strategy at the physiological level. In vivo systems offer the possibility of investigating not only the effects of specific genetic modifications or treatments in selected tissues and organs, but also to elucidate compensatory allostatic mechanisms induced to maintain the homeostasis of the whole system. A key challenge for systems biology is to characterize different systems’ responses in the context of activated pathways. One possible strategy is based on reconstruction of tissue specific pathways using lipidomics, or metabolomics in general, in combination with proteomic and transcriptomic profiles. This approach was applied to obese mouse model and revealed activation of multiple liver pathways that may lead to metabolic products, which may impair insulin sensitivity.