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The common transcriptional logic provided by BMAL1 and REV-ERB is thus a control system that coordinates entry into and exit from each 24-hr metabolic cycle. Although further research is necessary to elucidate the contribution of these clock genes in other tissue, perhaps in the adipose and the liver, the data presented herein are a powerful demonstration that the biological clock regulates metabolic gene programs during feeding and fasting. Underfeeding (e.g., the fasted state), the transcriptional logic of these clock genes dictates the partitioning of metabolism to exploit stored fuel, with REV-ERB-mediated repression likely favoring energy storage and fat accumulation. In contrast, the circadian day (fed state), BMAL1-dependent regulation of these clock targets would promote fatty acid oxidation and amino acid synthesis to replenish stores in anticipation of the feeding+activity phase, when glucose becomes the dominant fuel source (Fig 8).
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One of the drawbacks to this approach was that we needed to recompile every time we made even a small change to the code. This slowed everything else we were doing down and because we couldn't always have someone waiting for the application to finish building. 827ec27edc