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. 2023 Apr 12;24(8):7154. doi: 10.3390/ijms24087154

Figure 1.

Figure 1

Mechanism of the molecular clock. The above illustration shows that the early-timed breakfast at dawn activates the CLOCK: BMAL1 complex associated with SIRT1 and the transcription of PERs and CRYs. The resulting proteins PER (P) and CRY (C) form PER: CRY (C-P) dimers in the cytoplasm. Subsequently, PER: CRY dimers translocate back to the nucleus to repress CLOCK: BMAL1. The blockage of CLOCK: BMAL1 is reversed by casein kinase I epsilon (CKIε). NAD+ activates SIRT1, which interacts with the CLOCK: BMAL1. In addition, AMPK positively interacts with SIRT1. CLOCK: BMAL1-driven transcription of PERs, CRYs, REV-ERBα, RORα genes, and PGC-1α promotes the expression of tissue-specific clock-controlled genes. It leads to the upregulation of β-cell insulin secretion, L-cell postprandial incretin GLP-1 response, and the increase of GLUT4 activity and muscle glucose uptake. The clock gene-driven nocturnal hepatic glucose production promotes glycogenolysis and gluconeogenesis in the first and second part of the nocturnal resting phase. PGC-1α plays a role in lipid metabolism (lipogeneses and nocturnal lipolysis.