Cell Reports (Mar 2018)
A Diurnal Rhythm in Brown Adipose Tissue Causes Rapid Clearance and Combustion of Plasma Lipids at Wakening
- Rosa van den Berg,
- Sander Kooijman,
- Raymond Noordam,
- Ashna Ramkisoensing,
- Gustavo Abreu-Vieira,
- Lauren L. Tambyrajah,
- Wieneke Dijk,
- Philip Ruppert,
- Isabel M. Mol,
- Barbara Kramar,
- Rosanna Caputo,
- Laura Sardón Puig,
- Evelien M. de Ruiter,
- Jan Kroon,
- Menno Hoekstra,
- Ronald J. van der Sluis,
- Onno C. Meijer,
- Ko Willems van Dijk,
- Linda W.M. van Kerkhof,
- Constantinos Christodoulides,
- Fredrik Karpe,
- Zachary Gerhart-Hines,
- Sander Kersten,
- Johanna H. Meijer,
- Claudia P. Coomans,
- Diana van Heemst,
- Nienke R. Biermasz,
- Patrick C.N. Rensen
Affiliations
- Rosa van den Berg
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
- Sander Kooijman
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 7LE, UK; Corresponding author
- Raymond Noordam
- Department of Gerontology and Geriatrics, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
- Ashna Ramkisoensing
- Department of Molecular Cell Biology, Division of Neurophysiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
- Gustavo Abreu-Vieira
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
- Lauren L. Tambyrajah
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
- Wieneke Dijk
- Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, 6708 WE Wageningen, the Netherlands
- Philip Ruppert
- Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, 6708 WE Wageningen, the Netherlands
- Isabel M. Mol
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
- Barbara Kramar
- Department of Neuroscience and Pharmacology, Section for Metabolic Receptology, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200 Copenhagen, Denmark
- Rosanna Caputo
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
- Laura Sardón Puig
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
- Evelien M. de Ruiter
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
- Jan Kroon
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
- Menno Hoekstra
- Department of Biopharmaceutics, Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, the Netherlands
- Ronald J. van der Sluis
- Department of Biopharmaceutics, Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, the Netherlands
- Onno C. Meijer
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
- Ko Willems van Dijk
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
- Linda W.M. van Kerkhof
- Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, the Netherlands
- Constantinos Christodoulides
- Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 7LE, UK
- Fredrik Karpe
- Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 7LE, UK
- Zachary Gerhart-Hines
- Department of Neuroscience and Pharmacology, Section for Metabolic Receptology, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200 Copenhagen, Denmark
- Sander Kersten
- Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, 6708 WE Wageningen, the Netherlands
- Johanna H. Meijer
- Department of Molecular Cell Biology, Division of Neurophysiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
- Claudia P. Coomans
- Department of Molecular Cell Biology, Division of Neurophysiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
- Diana van Heemst
- Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 7LE, UK
- Nienke R. Biermasz
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
- Patrick C.N. Rensen
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
- Journal volume & issue
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Vol. 22,
no. 13
pp. 3521 – 3533
Abstract
Summary: 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. : van den Berg et al. show a strong circadian rhythm in fatty acid uptake by brown adipose tissue that peaks at wakening regardless of the light exposure period. Consequently, postprandial lipid handling by brown adipose tissue is highest at wakening, resulting in the lowest postprandial plasma lipid excursions. Keywords: circadian rhythm, diurnal rhythm, brown adipose tissue, triglycerides, fatty acids, lipoprotein lipase, angiopoietin-like 4, postprandial lipid response, APOE∗3-Leiden.CETP mice
