The circadian clock controls metabolic and physiological processes through finely tuned molecular mechanisms. The clock is remarkably plastic and adapts to exogenous "zeitgebers," such as light and nutrition. How a pathological condition in a given tissue influences systemic circadian homeostasis in other tissues remains an unanswered question of conceptual and biomedical importance. Here, we show that lung adenocarcinoma operates as an endogenous reorganizer of circadian metabolism. High-throughput transcriptomics and metabolomics revealed unique signatures of transcripts and metabolites cycling exclusively in livers of tumor-bearing mice. Remarkably, lung cancer has no effect on the core clock but rather reprograms hepatic metabolism through altered pro-inflammatory response via the STAT3-Socs3 pathway. This results in disruption of AKT, AMPK, and SREBP signaling, leading to altered insulin, glucose, and lipid metabolism. Thus, lung adenocarcinoma functions as a potent endogenous circadian organizer (ECO), which rewires the pathophysiological dimension of a distal tissue such as the liver. PAPERCLIP.

Lung Adenocarcinoma Distally Rewires Hepatic Circadian Homeostasis

The fruit fly Drosophila melanogaster is an established model organism in chronobiology, because genetic manipulation and breeding in the laboratory are easy. The circadian clock neuroanatomy in D. melanogaster is one of the best-known clock networks in insects and basic circadian behavior has been characterized in detail in this insect. Another model in chronobiology is the honey bee Apis mellifera, of which diurnal foraging behavior has been described already in the early twentieth century. A. mellifera hallmarks the research on the interplay between the clock and sociality and complex behaviors like sun compass navigation and time-place-learning. Nevertheless, there are aspects of clock structure and function, like for example the role of the clock in photoperiodism and diapause, which can be only insufficiently investigated in these two models. Unlike high-latitude flies such as Chymomyza costata or D. ezoana, cosmopolitan D. melanogaster flies do not display a photoperiodic diapause. Similarly, A. mellifera bees do not go into "real" diapause, but most solitary bee species exhibit an obligatory diapause. Furthermore, sociality evolved in different Hymenoptera independently, wherefore it might be misleading to study the social clock only in one social insect. Consequently, additional research on non-model insects is required to understand the circadian clock in Diptera and Hymenoptera. In this review, we introduce the two chronobiology model insects D. melanogaster and A. mellifera, compare them with other insects and show their advantages and limitations as general models for insect circadian clocks.

/pdf/model-and-non-model-insects-in-chronobiology-3dnvxqo7sa.pdf

Model and Non-model Insects in Chronobiology

O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes Recent studies showed that O-linked N-acetylglucosamine(GlcNAc) transferase(OGT) mediated O-Glc NAcylation of histone H2B Ser 112(H2B S112 Glc NAcylation) plays an important role in gene transcription However, the role of this histone modification in DNA damage response has not been studied yet In this study, we found that OGT and OGT mediated H2B S112 Glc NAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stressinducing agents OGT mediated H2B S112 GlcNAcylation increased locally upon the induction of double-strand breaks(DSBs), and depletion of OGT or overexpression of H2B S112A mutant impaired homologous recombination(HR) and nonhomologous end-joining(NHEJ) Mechanistically, H2B S112 GlcNAcylation could bind Nijmegen breakage syndrome 1(NBS1) and regulate NBS1 foci formation Taken together, our results demonstrate a new function of histone O-GlcNAcylation in DNA damage response(DDR)

OGT Mediated Histone H2B $112 GlcNAcylation Regulates DNA Damage Response

Many behaviors exhibit ~24-h oscillations under control of an endogenous circadian timing system that tracks time of day via a molecular circadian clock. In the fruit fly, Drosophila melanogaster, ...

Central and Peripheral Clock Control of Circadian Feeding Rhythms

The integration of circadian and metabolic signals is essential for maintaining robust circadian rhythms and ensuring efficient metabolism and energy use. Using Drosophila as an animal model, we showed that cellular protein O-linked N-acetylglucosaminylation (O-GlcNAcylation) exhibits robust 24-hour rhythm and is a key post-translational mechanism that regulates circadian physiology. We observed strong correlation between protein O-GlcNAcylation rhythms and clock-controlled feeding-fasting cycles, suggesting that O-GlcNAcylation rhythms are primarily driven by nutrient input. Interestingly, daily O-GlcNAcylation rhythms were severely dampened when we subjected flies to time-restricted feeding (TRF) at unnatural feeding time. This suggests the presence of a clock-regulated buffering mechanism that prevents excessive O-GlcNAcylation at non-optimal times of the day-night cycle. We found that this buffering mechanism is mediated by glutamine-fructose-6-phosphate amidotransferase (GFAT) activity, which is regulated through integration of circadian and metabolic signals. Finally, we generated a mathematical model to describe the key factors that regulate daily O-GlcNAcylation rhythm.

/pdf/hexosamine-biosynthetic-pathway-integrates-circadian-and-ljq6ltj162.pdf

Hexosamine biosynthetic pathway integrates circadian and metabolic signals to regulate daily rhythms in protein O-linked N-acetylglucosaminylation

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Hexosamine biosynthetic pathway integrates circadian and metabolic signals to regulate daily rhythms in protein O-linked N-acetylglucosaminylation