Role of PPARα in the control of torpor through FGF21-NPY pathway: From circadian clock to seasonal change in mammals.

In nature, hibernating animals encounter fasting, cold temperature and short day seasonally. Torpor is a state of decreased physiological activity in an animal, usually characterized by a reduced body temperature and rate of metabolism to adapt such a severe environment. Ablation of the central clock synchronizer, the suprachiasmatic nucleus in brain, abolishes torpor, a hibernation-like state, implicating the circadian clock involved in this seasonal change.

Circadian clock, cancer and lipid metabolism.

Genetic analysis has revealed that mammalian circadian oscillator is driven by a cell autonomous transcription/translation-based negative feedback loop, wherein positive elements (CLOCK and BMAL1) induce the expression of negative regulators (Periods, CRY1 and CRY2) that inhibit the transactivation of positive regulators. Recent research reveals that this clock feedback loop affects many aspects of our physiology, such as cell cycle and lipid metabolism. In this review, I summarize the molecular links between the circadian clock mechanism and the cell cycle, and between the clock and lipid metabolism.