Circadian regulation of lipid mobilization in white adipose tissues

  1. Henrik Oster1,2,*
  1. 1:Circadian Rhythms Group Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany
  2. 2:Medical Department I, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany
  1. *: Corresponding author: henrik.oster{at}uksh.de

Abstract

In mammals, a network of circadian clocks regulates 24-hr rhythms of behavior and physiology. Circadian disruption promotes obesity and the development of obesity-associated disorders, but it remains unclear to which extent peripheral tissue clocks contribute to this effect. To reveal the impact of the circadian timing system on lipid metabolism, blood and adipose tissue samples from wild-type, ClockΔ19 and Bmal1-/- circadian mutant mice were subjected to biochemical assays and gene expression profiling. We show diurnal variations in lipolysis rates and release of free fatty acids (FFAs) and glycerol into the blood correlating with rhythmic regulation of two genes encoding the lipolysis pacemaker enzymes adipose triglyceride lipase (Atgl) and hormone-sensitive lipase (Hsl) by self-sustained adipocyte clocks. Circadian clock mutant mice show low and non-rhythmic FFA and glycerol blood content together with decreased lipolysis rates and increased sensitivity to fasting. Instead circadian clock disruption promotes the accumulation of triglycerides in WAT, leading to increased adiposity and adipocyte hypertrophy. In summary, circadian modulation of lipolysis rates regulates the availability of lipid-derived energy during the day, suggesting a role for WAT clocks in the regulation of energy homeostasis.

  • Received October 20, 2012.
  • Accepted February 14, 2013.

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