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Control strategies in systemic metabolism

Abstract

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.

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Fig. 1: The metabolic economy.
Fig. 2: Metabolic producers and consumers.
Fig. 3: Metabolic control circuits.
Fig. 4: Three strategies of metabolic control.
Fig. 5: Consumers’ priorities and competition.
Fig. 6: Relationships between metabolic control strategies and the evolution of homeostasis.

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Acknowledgements

The authors thank all members of the laboratory of R.M. for helpful discussions and development of the ideas presented in this review. J.J.Y. is supported by the Yale School of Medicine Medical Scientist Training Program training grant (GM007205). R.M. is supported by the Howard Hughes Medical Institute, the Blavatnik Family Foundation and a grant from the NIH (R01 AI144152-01).

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R.M. conceived the original idea for this review, which was researched by and further developed with J.Y. J.Y. and R.M. co-wrote the manuscript and created the figures.

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Correspondence to Ruslan Medzhitov.

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Ye, J., Medzhitov, R. Control strategies in systemic metabolism. Nat Metab 1, 947–957 (2019). https://doi.org/10.1038/s42255-019-0118-8

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