Abstract
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.
Highlights
How organisms keep track of timeThe rotation of the Earth around its own axis creates a precise 24-h natural light and dark rhythm
Two isoforms of OPN4 are expressed in a subset of intrinsically photosensitive retinal ganglion cells [12, 16, 17] and are further subdivided into five categories [16–18]
Upon photon capture by intrinsically photosensitive retinal ganglion cells (ipRGCs), light information is transformed into electric pulses that travel through the retinohypothalamic tract (RHT), a monosynaptic pathway that innervates the ventromedial portion of the suprachiasmatic nucleus (SCN) containing vasoactive intestinal polypeptide
Summary
The rotation of the Earth around its own axis creates a precise 24-h natural light and dark rhythm. A third loop consists of BMAL1/CLOCK driving the expression of the PAR-bZip (proline and acidic amino acid-rich basic leucine zipper) transcription factor DBP (Albumin D‐site Binding Protein) that interacts at D-box enhancer regions with the repressor NFIL3 (Nuclear Factor, Interleukin‐3 Regulated, known as E4BP4), expression of which is driven through the REVERB/ROR loop. Such D-box elements are found in the Per promoter regions (Fig. 1). More than 40% of all protein coding genes display rhythmic transcription in at least one tissue of the body [24]
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