Role of the circadian clock gene Per2 in adaptation to cold temperature
Ripperger, Jürgen Alexander
Date of Issue2013
The Lee Kong Chian School of Medicine
Adaptive thermogenesis allows mammals to resist to cold. For instance, in brown adipose tissue (BAT) the facultative uncoupling of the proton gradient from ATP synthesis in mitochondria is used to generate systemic heat. However, this system necessitates an increase of the Uncoupling protein 1 (Ucp1) and its activation by free fatty acids. Here we show that mice without functional Period2 (Per2) were cold sensitive because their adaptive thermogenesis system was less efficient. Upon cold-exposure, Heat shock factor 1 (HSF1) induced Per2 in the BAT. Subsequently, PER2 as a co-activator of PPARα increased expression of Ucp1. PER2 also increased Fatty acid binding protein 3 (Fabp3), a protein important to transport free fatty acids from the plasma to mitochondria to activate UCP1. Hence, in BAT PER2 is important for the coordination of the molecular response of mice exposed to cold by synchronizing UCP1 expression and its activation.
DRNTU::Science::Biological sciences::Molecular biology
© 2013 Elsevier GmbH. This paper was published in Molecular Metabolism and is made available as an electronic reprint (preprint) with permission of Elsevier GmbH. The paper can be found at the following official DOI: [http://dx.doi.org/10.1016/j.molmet.2013.05.002]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.