Physiology

Tick Tock Liver Clock

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Science  17 Oct 2008:
Vol. 322, Issue 5900, pp. 349
DOI: 10.1126/science.322.5900.349c

Rodents harbor an endogenous cycling clock with a period of about 24 hours. The so-called “master clock” in the brain is set by light, whereas subsidiary “peripheral” clocks are entrained by the animals' feeding schedule. Without these clocks, animals show impaired sleeping, eating, and activity rhythms, as well as pronounced problems in energy balance and glucose homeostasis. To understand how circadian clocks participate in glucose homeostasis, Lamia et al. selectively inactivated the clock in the liver by engineering mice with a conditional knockout allele for an essential clock component, the protein Bmal. These mice were unable to maintain steady levels of blood glucose, showing a drop in glucose during the fasting segment of their daily feeding cycle. This drop is normally prevented by a daily increase in the transcription of glucose transporter 2, a gene coding for the membrane protein that exports stored glucose from the liver into the blood. Other similarly regulated genes contribute to metabolic homeostasis. Thus, the liver circadian clock, entrained by the feeding cycle, has daily cycles of metabolic activity that ensure a steady supply of energy for the organism. — KK

Proc. Natl. Acad. Sci. U.S.A. 105, 15172 (2008).

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