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Angiopoietin-like 4 dictates the day-night rhythm of metabolic brown adipose tissue activity

PUBLISHED June 24, 2023 (DOI: https://doi.org/10.54985/peeref.2306p7202701)



Robin Van Eenige1 , Wietse In Het Panhuis1 , Milena Schönke1 , Céline Jouffe2 , Thomas Devilee1 , Ricky Siebeler1 , Trea Streefland1 , Hetty Sips1 , Amanda Pronk1 , Ruben Vorderman3 , Hailiang Mei3 , Jan Bert Van Klinken4 , Michel Van Weeghel4 , Nina Uhlenhaut2 , Sander Kersten5 , Patrick Rensen1 , Sander Kooijman1
  1. Dept. Medicine, Div. Endocrinology Einthoven Lab. for Exp. Vasc. Med., LUMC, Leiden, The Netherlands
  2. Inst. for Diab. and Endo., Helmholtz Diab. Center and German Center for Diab. Res., Munich, Germany
  3. Dept. Biomedical Data Sciences, LUMC, Leiden, The Netherlands
  4. Laboratory Genetic Metabolic Diseases, Amsterdam UMC, Amsterdam, The Netherlands
  5. Nutr., Metab. and Genom. Group, Div. Human Nutr., Wageningen University, Wageningen, The Netherlands

Conference / event

Dutch Translational Metabolism Conference, June 2022 (Wageningen, Netherlands)

Poster summary

Brown adipose tissue (BAT) burns fatty acids (FAs) to produce heat, and interestingly shows a strong day-night rhythm in glucose and triglyceride (TG)-derived FA-uptake (Van den Berg, Cell Rep 2018), peaking around wakening. Here we aimed to gain insight in the diurnal regulation of metabolic BAT activity. BAT was collected from chow-fed male C57BL/6J mice at 3-hour intervals throughout the day, and RNA-sequencing, chromatin immunoprecipitation (ChIP)-sequencing, and lipidomics analyses were performed. Knockout and overexpression models were used to study causal relationships in diurnal lipid handling by BAT. Our findings highlight involvement of PPARγ and a crucial role of angiopoietin-like 4 (ANGPTL4) in mediating the day-night rhythm of TG-derived FA-uptake by BAT, and implicate that time of day should be considered when studying the metabolic benefits of targeting brown fat.


Angiopoietin-like 4, Brown adipose tissue, Circadian/diurnal rhythms, Lipoprotein lipase, Peroxisome proliferator-activated receptor gamma, Transcriptomics

Research areas

Molecular and Cellular Biosciences, Medicine


  1. Khedoe, J Lipid Res 2015
  2. Becher, Nat Med 2021
  3. Herz, Diabetes 2021
  4. Van den Berg, Cell Rep 2018
  5. Van Eenige, Mol Metab 2022


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Supplemental files

No data provided

Additional information

Competing interests
No competing interests were disclosed.
Data availability statement
The datasets generated during and / or analyzed during the current study are available from the corresponding author on reasonable request.
Creative Commons license
Copyright © 2023 Van Eenige et al. This is an open access work distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Van Eenige, R., In Het Panhuis, W., Schönke, M., Jouffe, C., Devilee, T., Siebeler, R., Streefland, T., Sips, H., Pronk, A., Vorderman, R., Mei, H., Van Klinken, J., Van Weeghel, M., Uhlenhaut, N., Kersten, S., Rensen, P., Kooijman, S. Angiopoietin-like 4 dictates the day-night rhythm of metabolic brown adipose tissue activity [not peer reviewed]. Peeref 2023 (poster).
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