Circadian clock-coordinated hepatic lipid metabolism: only transcriptional regulation

Abstract

By regulating the metabolism of fatty acids, carbohydrates, and xenobiotic, the mammalian circadian clock plays a fundamental role on the liver physiology. At present, it is supposed that the circadian clock regulates metabolism mostly by regulating the expression of liver enzymes at the transcriptional level. However, recent evidences suggest that some signaling pathways synchronized by the circadian clock can also influence metabolism at a post-transcriptional level. In this context, we have recently shown that the circadian clock synchronizes the rhythmic activation of the IRE1α pathway in the endoplasmic reticulum. The absence of circadian clock perturbs this secondary clock, provokes deregulation of endoplasmic reticulum-localized enzymes, and leads to impaired lipid metabolism. We will describe here the additional pathways synchronized by the clock and discussed the influence of the circadian clock-controlled feeding rhythm on them.

Circadian clocks are operative in virtually all light-sensitive organisms, including cyanobacteria, fungi, plants, protozoans and metazoans. These timing devices allow their possessors to adapt their physiological needs to the time of day in an anticipatory way. In mammals, circadian pacemakers regulate many systemic processes, such as sleep-wake cycles, body temperature, heartbeat, and many physiological outputs conducted by peripheral organs, such as liver, kidney and the digestive tract [1]. On the basis of surgical ablation and transplantation experiments, it was established that the suprachiasmatic nucleus (SCN) in the hypothalamus coordinates most of these daily rhythms [2], probably through both synaptic connections and humoral signals [3]. Interestingly, self-sustained and cell-autonomous molecular oscillators do not only exist in pacemaker cells such as SCN neurons, but are also operative in most peripheral, non-neuronal cell types [4]. These peripheral oscillators participate in the circadian control https://www.aging-us.com/article/100123/text

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Misha Blagosklonny
“A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This paper was released back in 2018 by Oncotarget and completed by several experts from Hollywood Private Hospital, Edith Cowan University, Dermatology Specialist Group, St. John of God Hospital and The University of Western Australia. The introduction of the study discusses “recent data shows that Australians are four times more likely to develop a cancer of the skin than any other type of cancer”, and shares an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
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Misha Blagosklonny