Loss of Nocturnin, a circadian deadenylase, confers resistance to hepatic steatosis and diet-induced obesity

• Published in: Proceedings of the National Academy of Sciences - PNAS 2007-06, Vol.104 (23), p.9888-9893
• Main Authors: Green, Carla B, Douris, Nicholas, Kojima, Shihoko, Strayer, Carl A, Fogerty, Joseph, Lourim, David, Keller, Susanna R, Besharse, Joseph C
• Format: Article
• Language: English
• Subjects: Animals; Azo Compounds; Biological Clocks - genetics; Biological Clocks - physiology; Biological Sciences; Biology; Blood Glucose; body fat; Body Temperature; Body Weight; body weight changes; Circadian rhythm; Circadian Rhythm - genetics; Circadian Rhythm - physiology; Diabetes; Diet; Energy Metabolism - genetics; Energy Metabolism - physiology; fatty liver; Fatty Liver - genetics; Feeding Behavior - physiology; gene expression; Gene Expression Regulation - genetics; Gene Expression Regulation - physiology; genes; Genotypes; Gluconeogenesis - genetics; Gluconeogenesis - physiology; High fat diet; Immunity, Innate - genetics; Insulin; Insulin - blood; Lipid metabolism; Lipids; Lipids - blood; Liver; Mammals; Messenger RNA; Mice; Mice, Knockout; Nocturnin; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; obesity; Obesity - genetics; Phenotypes; Reverse Transcriptase Polymerase Chain Reaction; Ribonucleic acid; RNA; RNA deadenylase; Suprachiasmatic Nucleus - physiology; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0702448104

The mammalian circadian system consists of a central oscillator in the suprachiasmatic nucleus of the hypothalamus, which coordinates peripheral clocks in organs throughout the body. Although circadian clocks control the rhythmic expression of a large number of genes involved in metabolism and other aspects of circadian physiology, the consequences of genetic disruption of circadian-controlled pathways remain poorly defined. Here we report that the targeted disruption of Nocturnin (Ccrn4l) in mice, a gene that encodes a circadian deadenylase, confers resistance to diet-induced obesity. Mice lacking Nocturnin remain lean on high-fat diets, with lower body weight and reduced visceral fat. However, unlike lean lipodystrophic mouse models, these mice do not have fatty livers and do not exhibit increased activity or reduced food intake. Gene expression data suggest that Nocturnin knockout mice have deficits in lipid metabolism or uptake, in addition to changes in glucose and insulin sensitivity. Our data support a pivotal role for Nocturnin downstream of the circadian clockwork in the posttranscriptional regulation of genes necessary for nutrient uptake, metabolism, and storage.