Aging selectively dampens oscillation of lipid abundance in white and brown adipose tissue

Abstract

Lipid metabolism is under the control of the circadian system and circadian dysregulation has been linked to obesity and dyslipidemia. These factors and outcomes have also been associated to, or affected by, the process of aging. Here, we investigated whether murine white (WAT) and brown (BAT) adipose tissue lipids exhibit rhythmicity and if this is affected by aging. To this end, we have measured the 24 hour lipid profiles of WAT and BAT using a global lipidomics analysis of >1100 lipids. We observed rhythmicity in nearly all lipid classes including glycerolipids, glycerophospholipids, sterol lipids and sphingolipids. Overall, ~22% of the analyzed lipids were considered rhythmic in WAT and BAT. Despite a general accumulation of lipids upon aging the fraction of oscillating lipids decreased in both tissues to 14% and 18%, respectively. Diurnal profiles of lipids in BAT appeared to depend on the lipid acyl chain length and this specific regulation was lost in aged mice. Our study revealed how aging affects the rhythmicity of lipid metabolism and could contribute to the quest for targets that improve diurnal lipid homeostasis to maintain cardiometabolic health during aging.

Chronic Jetlag Alters the Landscape of the Pancreatic Lipidome

“…There are now multiple studies across several organ systems demonstrating diurnal variations of lipids in response to different conditions. 12,13,[31][32][33] In our study, which was the first to examine the effects of a CJ protocol on mouse pancreatic transcriptome, we found that several lipid metabolism pathways were altered and genes in these pathways exhibited a shift in the phase (peak 24-hour expression) of their expression. 14 Therefore, we sought to first understand whether there are diurnal variations in the pancreatic lipidome and subsequently whether there are changes in the pancreatic lipidome in response to CJ conditions.…”

“…In another study analyzing the effects of aging in the lipidome of white and brown adipose tissues, the authors noted an increase in DGs but not TGs in aging mice. 12 Similarly, another study investigating human skeletal muscle showed that the majority of rhythmic lipids were TGs and DGs. 31 When examining the results of our BioPAN analysis, we found that one possible mechanism for increasing pools of available DG was through suppression of PC and PE synthesis.…”

“…Thus, the core circadian clock is clearly implicated in the regulation of lipid metabolism. In further support of this link, analysis of white and brown fat of young and old mice revealed that 14% to 21% of the fat lipidome was found to be rhythmic, indicating circadian control 12 . Moreover, shotgun lipidomics experiments in the liver (similarly metabolic organ to the pancreas) have demonstrated that 17% of the liver lipidome measured was rhythmically expressed 13 .…”

“…In further support of this link, analysis of white and brown fat of young and old mice revealed that 14% to 21% of the fat lipidome was found to be rhythmic, indicating circadian control. 12 Moreover, shotgun lipidomics experiments in the liver (similarly metabolic organ to the pancreas) have demonstrated that 17% of the liver lipidome measured was rhythmically expressed. 13 Our laboratory recently carried out a whole-pancreas transcriptomic evaluation of WT mice subjected to 1 month of a chronic jetlag (CJ) protocol that mimics human shiftwork.…”

A multi‐level assessment of the bidirectional relationship between aging and the circadian clock

“…A recent study shows that aging severely affects the levels and rhythmicity of lipids in brown and white adipose tissue, indicating a disturbed lipid metabolism (Held et al . 2020). Aging is also associated with changes in rhythmic gene expression in the liver, affecting genes associated with metabolic processes (Sato et al., 2017).…”