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. 2020 May 15;23(6):101161. doi: 10.1016/j.isci.2020.101161

Figure 2.

Figure 2

TRE Regulation of Peripheral Circadian Clocks

TRE can reprogram circadian clock in the fasting state via AMPK and in the fed state via mTOR.

(A) In the fed state, nutrient availability activates mTOR. Activated mTOR induces Cry, which represses Clock:Bmal1.

(B) In the fasting state, nutrient depletion activates AMPK that directly and indirectly enhances phosphorylation on cry, and per. Phosphorylation is key for degradation of these proteins. Next, AMPK can activate SIRT1 activity via NAMPT. SIRT1 binds with clock:bmal1 and represses the transcription of per2. The acetyltransferase activity of clock is counteracted by SIRT1. Blue arrows represent core clock machinery, green arrows represent effect of TRE. AMPK:,AMP-activated protein kinase; bmal1, brain and muscle arnt like 1; CCG, clock-controlled genes; CK, casein kinase; clock, circadian locomotor output cycle kaput; cry, cryptochrome; mTOR, mechanistic target of rapamycin; NAD, nicotinamide adenine dinucleotide; NAMPT, nicotinamide phosphoribosyl transferase; per, period; SIRT1, sirtuin1.