The food entrainable oscillator studied by DNA microarrays: What is the liver doing during food anticipatory activity?

Abstract

The food-entrainable oscillator (FEO) is a circadian clock that elicits behavioral responses based on physiological associations between selected brain areas and peripheral tissues. The liver plays an important role in the control of food intake and in the processing of nutrients. Significant adjustments occur in the metabolic status of the liver during the onset and the manifestation of the FEO. We have used DNA microarrays to identify the expression levels of hundreds of hepatic genes in rats under restricted feeding schedules. The results revealed that 64 out of 1353 transcripts changed significantly in the liver (54 up-regulated and 10 down-regulated), coincident with food anticipatory activity. These data suggest an increased protein synthesis and metabolism. They also imply a predominant role of mitochondria and peroxisomes in the catabolic processing of lipids. Another group of genes with FEO-induced modified transcription was related to the hepatocyte redox state of thiol moieties. Interestingly, several liver-secreted factors related to the acute phase response (APR) presented an enhanced transcription during food anticipation. Taken together, these results make it possible to foresee some of the characteristics of the homeorethic status that the liver adopts when the FEO is expressed.

Keywords:

• FEO
• food restriction
• food-anticipatory activity
• circadian rhythms
• metabolic regulation
• food intake
• hepatic physiology
• transcriptome profile

Acknowledgements

The authors are indebted to Dr. Carmen Aceves, Instituto de Neurobiología, UNAM, for technical advice on mRNA purification methodology, and to José Luis Santillán-Torres, Simón Guzmán-León and Lorena Chávez González, Microarray Unit, Instituto de Fisiología Celular, for technical assistance in the microarray determinations. We also acknowledge Dr. Anaid Antaramián, Unidad de Biología Molecular, INB, for her useful advice on elaboration of the experimental protocol. This work was supported by Grant IN222102 from Dirección General de Asuntos del Personal Académico to M.D.-M.