Lipidomics Analyses Reveal Temporal and Spatial Lipid Organization and Uncover Daily Oscillations in Intracellular Organelles

Abstract

Cells have evolved mechanisms to handle incompatible processes through temporal organization by circadian clocks and by spatial compartmentalization within organelles defined by lipid bilayers. Recent advances in lipidomics have led to identification of plentiful lipid species, yet our knowledge regarding their spatiotemporal organization is lagging behind. In this study, we quantitatively characterized the nuclear and mitochondrial lipidome in mouse liver throughout the day, upon different feeding regimens, and in clock-disrupted mice. Our analyses revealed potential connections between lipid species within and between lipid classes. Remarkably, we uncovered diurnal oscillations in lipid accumulation in the nucleus and mitochondria. These oscillations exhibited opposite phases and readily responded to feeding time. Furthermore, we found that the circadian clock coordinates the phase relation between the organelles. In summary, our study provides temporal and spatial depiction of lipid organization and reveals the presence and coordination of diurnal rhythmicity in intracellular organelles.

Lipidomics reveals diurnal lipid oscillations in human skeletal muscle persisting in cellular myotubes cultured in vitro

“…5), similar to previous analyses in mouse liver (17). Whereas such changes in amplitude are smaller than for diurnal transcript oscillations, they represent substantial differences in membrane homeostasis across 24 h.…”

“…This effect was characteristic for long and very long chain PC and SM lipids, which were highly synchronized in both skeletal muscle and primary myotubes, whereas other PLs like PE did not show this preference. Remarkably, a correlation based on chain length was also observed for long and very long chain PC and SM species in WT and Per1/2 KO mice whereas the contribution of desaturation was less prominent (17). Consistent with this observation is the rhythmic gene expression of ELOVL5, ACSL4, and ACSL5 in human skeletal muscle tissue, whose peak of expression correlated with peak levels of very long chain PC and SM lipids ( Fig.…”

“…Recent studies by Asher and coworkers identified that 17% of lipid metabolites oscillate when assessed in whole liver (16) whereas separate analyses of liver nuclei and mitochondria identified 34% and 31% of oscillating lipids, respectively, with distinct circadian phases between these organelles (17). However, it should be noted that participants in this study were confined to a semirecumbent position throughout the testing day while, in the mouse liver study, the data were collected from mice freely moving until the sampling point.…”

“…However, substantial differences in their composition and peak phase of oscillation were observed, suggesting that both endogenous clocks and fasting-feeding cycles contribute to the observed profile (16). Furthermore, quantitative characterization of the nuclear and mitochondrial lipidome of mouse liver uncovered daily lipid oscillations with distinct phases in these intracellular organelles (17).…”

Liver size: Waning by day, Waxing by Night

“…In this context, it was recently shown that the lipid composition of the nucleus and mitochondria exhibit daily rhythms. (8) The current study and the emerging open questions carry wide implications on our basic understanding of liver function in health and disease.…”