For those that don't want to read the whole thing (it's long)
It is well known that circadian clock regulates cellular metabolism. There has been considerable interest in studying the crosstalk between metabolism and the circadian clock[Invalid Link Removed]. However, it is not clear how various metabolic signals feed back into the clock mechanism. In the current study, we focused on the role of mTOR signaling in regulating the endogenous circadian clock function. Following our clock gene discovery through functional genomics, we employed an integrated approach combining genetic and pharmacological methods and examined the mTOR effects on circadian rhythms at multiple levels of biological organization, including fibroblasts, hepatocytes, adipocytes, the liver, the SCN, and the whole organism. We found that, while mTOR activation speeds up the clock oscillations (i.e. shorter period), mTOR inhibition lengthens circadian period. These phenotypes are consistent across multiple cell and tissue types including the central and peripheral oscillators. Moreover, mTOR also regulates rhythm amplitude: whereas mTOR inhibition dampens the amplitude, its activation increases the amplitude. Thus, certain level of mTOR activities appears to be required to maintain normal circadian oscillations in the SCN and peripheral oscillators.
