Abstract
Circadian rhythms are generated by endogenous clocks and regulate the daily fluctuations of biochemical, behavioral, and physiological rhythms. It has been shown that the disruption of circadian rhythms affects many physiological events including metabolism, however, the molecular mechanisms that connect circadian clocks and metabolism are poorly understood. The Nocturnin (Ccrn4l) gene encodes a deadenylase, which removes polyA tail and destabilizes target mRNA expression post-transcriptionally. The expression of mouse Nocturnin (mNoc) mRNA is rhythmic in many tissues, and peaks at early night. We found that the mice lacking mNoc gene were resistant to diet-induced obesity and remained lean when they were fed with High-Fat diet. The mutant mice do not exhibit increased activity or reduced food intake. Furthermore, KO mice had lower body temperatures, although metabolic rates of these mutant mice remained same as WT. Finally we have observed altered expression patterns of many genes known to be involved in regulation of lipid synthesis or utilization. Our data indicate that Nocturnin has an important role in the pathway that connects circadian rhythms and metabolism perhaps through changes in lipid uptake or storage. Given that mNoc is a deadenylase, the most probable explanation for this lean phenotype would be alterations in post-transcriptional regulation of mRNAs involved in these processes. [J Physiol Sci. 2007;57 Suppl:S87]
