A Diurnal Rhythm in Brown Adipose Tissue Causes Rapid Clearance and Combustion of Plasma Lipids at Wakening

Abstract

Many favorable metabolic effects have been attributed to thermogenic activity of brown adipose tissue (BAT). Yet, time of day has rarely been considered in this field of research. Here, we show that a diurnal rhythm in BAT activity regulates plasma lipid metabolism. We observed a high-amplitude rhythm in fatty acid 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 lipoprotein lipase expression and low angiopoietin-like 4 expression by BAT. 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 mice as well as humans, postprandial lipid excursions were nearly absent at waking. We anticipate that diurnal BAT activity is an important factor to consider when studying the therapeutic potential of promoting BAT activity.

Melatonin multiple effects on brown adipose tissue molecular machinery

“…66,[75][76][77] Brown adipose tissue was shown to present a clear daily rhythm in its metabolic function and in Pgc1α gene expression and Ucp1 gene and protein expression that is fundamental for its thermogenic function. 26,56 The present BAT thermogenic pathway analysis throughout 24 hours in sub-thermoneutral conditions exhibited a haphazard Ucp1 gene expression in PINX rats, evidencing a nonrhythmic organization. In addition, this group presented a temporally displaced peak of UCP1 gene and protein expression, reinforcing this tissue possible inability to respond to future challenges.…”

Interplay between diet, exercise and the molecular circadian clock in orchestrating metabolic adaptations of adipose tissue

“…Indeed, TG-derived FA uptake in brown adipose tissue and thermogenic activity has been previously shown to be under the direct control of the SCN via the nuclear factor REV-ERBα (Gerhart-Hines et al 2013;Moran-Ramos et al 2017). While the circadian brown adipose tissue activity predicts the variation in plasma TG and FA level, and determines the postprandial handling of TGs in mice, this finding has not been corroborated in humans (van den Berg et al 2018).…”

“…Although the diurnal variation in brown adipose tissue activity did not influence blood glucose oscillations, a modest correlation was detected with the supraclavicular temperature response and glucose excursions among individuals with high brown adipose tissue abundance (Lee et al 2016). In male C57Bl/6J mice, brown adipose tissue also displays a diurnal rhythm in FA uptake, with increased TG-derived FA uptake at the onset of the active period (van den Berg et al 2018). These results indicate that photic cues and modulation of the light exposure duration influence brown adipose tissue activity in part via the central circadian clock machinery.…”

“…In male C57Bl/6J mice, brown adipose tissue also displays a diurnal rhythm in FA uptake, with increased TG‐derived FA uptake at the onset of the active period (van den Berg et al . ). These results indicate that photic cues and modulation of the light exposure duration influence brown adipose tissue activity in part via the central circadian clock machinery.…”

“…While the circadian brown adipose tissue activity predicts the variation in plasma TG and FA level, and determines the postprandial handling of TGs in mice, this finding has not been corroborated in humans (van den Berg et al . ).…”