Abstract 224: Biological Clock Strongly Regulates Brown Adipose Tissue Activity: Implications for Postprandial Triglyceride Metabolism

Abstract

Background: Brown adipose tissue (BAT) is an attractive anti-dyslipidemia target as it burns high amounts of triglycerides (TG) into heat. In humans, plasma TG levels display 24 h variation independent of food intake, indicating a strong regulation by the biological clock. We recently showed that prolonged day length decreases the uptake of TG by BAT. We now aimed to assess the 24 h rhythm of BAT activity, the effect of day length thereon, and the consequences for postprandial TG metabolism. Methods and Results: Male C57Bl/6J mice were exposed to short (8 h), regular (12 h), or long (16 h) days during 5 weeks. The rhythm of BAT was determined by its capacity to take up plasma TG-derived fatty acids (FA) at 6 time points during a 24 h period. Mice exposed to regular days displayed a remarkable diurnal pattern of TG-derived FA uptake from glycerol tri[ 3 H]oleate-labeled VLDL-like particles by BAT, but not by other tissues, reaching a peak [ 3 H]FA uptake at onset of dark. Short day length increased the amplitude of [ 3 H]FA uptake by 3-fold and advanced the peak of [ 3 H]FA uptake, again to onset of dark. Conversely, long day length delayed the peak to onset of dark. We next assessed whether BAT rhythmicity affects postprandial TG clearance in dyslipidemic APOE*3-Leiden.CETP mice. Mice were fed a western-type diet that were exposed to either a short (8 h) or long 16 h (long) days and gavaged with olive oil at several time points during the day. Irrespective of day length, postprandial TG excursion was virtually absent before the onset of dark (highest BAT activity) and high before onset of light (lowest BAT activity). Conclusion: Day length dictates a diurnal rhythm in TG-derived FA uptake capacity of BAT, thereby strongly determining postprandial TG metabolism. We propose that the diurnal variations in TG levels observed in humans may be explained by a diurnal rhythm in BAT activity.