Objectives: 
Brown adipose tissue (BAT) has emerged as a novel target to counteract cardiovascular disorders due to its capacity to increase energy expenditure through thermogenesis. In line with this, we found that activating BAT attenuates hypercholesterolemia and protects from atherosclerosis development in mice. Recently, we showed that circadian disruption by prolonged light exposure reduces BAT activity, resulting in adiposity (PNAS 2015). Since this finding implies the presence of a circadian component in BAT, we aimed to investigate whether BAT activity is rhythmic in mice and humans and to delineate underlying mechanisms. 

Methods & Results: 
In wild-type C57Bl/6J mice we injected glycerol tri[3H]oleate-labeled triglyceride-rich lipoprotein-like particles at 6 time points during a 24h period, and observed a high amplitude rhythm in [3H]oleate uptake by BAT that synchronized with the light/dark cycle. Highest uptake was found at the onset of the active period, which coincided with high LPL expression and low ANGPTL4 expression. In Angptl4-/- mice diurnal rhythmicity in BAT was absent. In APOE*3-Leiden.CETP mice diurnal rhythmicity in BAT activity determined the rate at which lipids were cleared from the circulation, thereby imposing the daily rhythm in plasma lipid concentrations. In both mice and humans, postprandial lipid excursions were nearly absent at waking. 

Conclusions: 
We found a strong diurnal rhythm in the triglyceride-derived fatty acid uptake by BAT, that is likely mediated by diurnal LPL activity and its inhibitor ANGPTL4. We anticipate that diurnal BAT activity could be an important factor in the therapeutic activation of BAT in cardiovascular disorders.

05 - A DIURNAL RHYTHM IN BROWN ADIPOSE TISSUE CAUSES RAPID CLEARANCE OF PLASMA LIPIDS AT WAKENING