de Assis, L.V.M., Oster, H. The circadian clock and metabolic homeostasis: entangled networks. Cell. Mol. Life Sci. (2021).


The circadian clock exerts an important role in systemic homeostasis as it acts a keeper of time for the organism. The synchrony between the daily challenges imposed by the environment needs to be aligned with biological processes and with the internal circadian clock. In this review, it is provided an in-depth view of the molecular functioning of the circadian molecular clock, how this system is organized, and how central and peripheral clocks communicate with each other. In this sense, we provide an overview of the neuro-hormonal factors controlled by the central clock and how they affect peripheral tissues. We also evaluate signals released by peripheral organs and their effects in the central clock and other brain areas. Additionally, we evaluate a possible communication between peripheral tissues as a novel layer of circadian organization by reviewing recent studies in the literature. In the last section, we analyze how the circadian clock can modulate intracellular and tissue-dependent processes of metabolic organs. Taken altogether, the goal of this review is to provide a systemic and integrative view of the molecular clock function and organization with an emphasis in metabolic tissues.


The circadian clock system is a complex and pervasive network that directly or indirectly controls a significant portion of all biological processes. Its role as a systemic regulator is seen in experimental models of gene silencing or knockout. Advancements in tissue-specific clock gene modulation has been important for a better understanding of tissue clock gene organization at both cellular as well as systemic levels. In addition to its molecular basis, the organizational aspects of the circadian clock network have received increased attention over the last years. Understanding how this biological timing machinery works at all levels of organization will be important to fully assess the consequences of circadian rhythm disruption by modern lifestyles and devise ways to prevent chronodisruption and treat associated diseases and conditions.

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