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SREBP-1 as a Transcriptional Integrator of Circadian and Nutritional Cues in the Liver

Unit on Temporal Gene Expression, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health

David Lange

Intramural Information Technology Program (IITP), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland

Ruben Baler

Unit on Temporal Gene Expression, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, baler{at}mail.nih.gov

Ana Anzulovich

Unit on Temporal Gene Expression, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health

The act of feeding in mammals can generate such powerful cues for peripheral organs that, under certain conditions, they can override the entraining signals coming from the clock in the brain. Restricting the feeding time to the inactivity period, for example, can completely and quickly reverse the rhythms of gene expression in the liver. This manipulation does not affect the central oscillator in the suprachiasmatic nucleus, which is phase-locked to the light-dark cycle, but does release the peripheral oscillations in the liver from central control. It seems reasonable to predict the existence of one or more immediate response systems designed to sense the need to acutely reverse the sequence of absorptive and postabsorptive phases in the liver. In this study, the authors monitored the posttranslational activation of the sterol response element binding proteins from a circadian point of view to evaluate the role they might play in the circadian organization of the liver transcriptome as well as in the reversal of hepatic physiology that accompanies diurnal restricted feeding. This study highlights a possible direct link between the immediate effects of food consumption on the level of key membrane and humoral factors and the expression status of a set of coordinately regulated target genes in the liver.

Key Words: circadian • liver • sterol response element binding protein • feeding behavior

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