Control strategies in systemic metabolism

Metabolic control systems coordinate myriad processes across the cellular, tissue and organismal levels to optimize the allocation of limited supplies across multiple, often competing, metabolic demands. As such, the regulation of metabolism can be analysed from the perspective of the economic theory of supply and demand. Here, we discuss how such analyses can provide new insights into the logic of metabolic control. In particular, we suggest that, in addition to being subject to well-appreciated homeostatic control, metabolism is subject to supply-driven and demand-driven controls, each operated by a dedicated set of signals throughout various physiological states, including inflammation. Furthermore, we argue that systemic homeostasis is a derived feature that evolved from the control systems that monitor metabolic supply and demand. The authors of this Review present a framework for understanding fundamental principles of metabolic regulation, drawing analogies between metabolic control and economic theory to discuss supply- and demand-driven metabolism.