Diurnal Oscillations in Liver Mass and Cell Size Accompany Ribosome Assembly Cycles

Abstract

Summary The liver plays a pivotal role in metabolism and xenobiotic detoxification, processes that must be particularly efficient when animals are active and feed. A major question is how the liver adapts to these diurnal changes in physiology. Here, we show that, in mice, liver mass, hepatocyte size, and protein levels follow a daily rhythm, whose amplitude depends on both feeding-fasting and light-dark cycles. Correlative evidence suggests that the daily oscillation in global protein accumulation depends on a similar fluctuation in ribosome number. Whereas rRNA genes are transcribed at similar rates throughout the day, some newly synthesized rRNAs are polyadenylated and degraded in the nucleus in a robustly diurnal fashion with a phase opposite to that of ribosomal protein synthesis. Based on studies with cultured fibroblasts, we propose that rRNAs not packaged into complete ribosomal subunits are polyadenylated by the poly(A) polymerase PAPD5 and degraded by the nuclear exosome.

Transcription factor activity rhythms and tissue-specific chromatin interactions explain circadian gene expression across organs

“…3A), which were associated with feeding and fasting rhythms (Gene Ontology analysis around the clock) (Methods). Indeed, ribosome biogenesis was up-regulated most strongly during the first 6 h of the feeding phase (from ZT12 to ZT18) (Jouffe et al 2013;Chauvin et al 2014), while insulin signaling was down-regulated during first 6 h of the fasting phase (from ZT0 to ZT6) (Ravnskjaer et al 2013), consistent with daily responses to nutrient fluctuations in liver (Sinturel et al 2017).…”

Liver size: Waning by day, Waxing by Night

“…A recent publication from the lab of Ueli Schibler showed that daily changes in actin dynamics in liver of mice are accompanied by pronounced size oscillations of mouse hepatocytes. (3) In a follow-up publication from the same lab published recently in Cell, Sinturel et al (4) demonstrated that these size changes are primarily regulated by feeding time.…”

“…Furthermore, a large body of work shows that hepatic cell size changes induced by hormones or osmotic gradients can have many pleiotropic effects on organ function, among others an increase in cell volume which inhibits proteolysis and stimulates global protein translation in liver cells, (5) effectively resulting in the same positive correlation between cell size and protein mass as in the present study. (4) At this point, however, we cannot exclude the possible involvement of other cellular mechanisms or molecular constituents in the process of hepatic cell size oscillations. It was recently reported that hepatic lipid composition exhibits feeding-dependent daily rhythms.…”

“…Earlier reports indicated that constraints from extracellular tissue might limit cell swelling, (5) whereas the present study moves the focus toward cell-specific differences in global translation efficiency. (4) Are the changes in cell size accompanied by alterations in the size and/or morphology of intracellular organelles? In this context, it was recently shown that the lipid composition of the nucleus and mitochondria exhibit daily rhythms.…”

Fat-Referenced MRI: Quanitaive MRI for Tissue Characterizaion and Volume Measurement

“…For instance edema can increase the water concentration significantly [86]. Another possible confounder is the daily variations in liver hydration [87,88]. In humans a daily variation of 20 % has been observed by ultra-sound [88].…”