Loss of Nocturnin, a circadian deadenylase, confers resistance to hepatic steatosis and diet-induced obesity.
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.
Green
Carla B
CB
Department of Biology, University of Virginia, Charlottesville, VA 22904, USA. cgb8b@virginia.edu
Douris
Nicholas
N
Kojima
Shihoko
S
Strayer
Carl A
CA
Fogerty
Joseph
J
Lourim
David
D
Keller
Susanna R
SR
Besharse
Joseph C
JC
D000818:Animals; D001391:Azo Compounds; D001683:Biological Clocks / Q000235:genetics / Q000502:physiology*; D001786:Blood Glucose; D001831:Body Temperature; D001835:Body Weight; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology; D005234:Fatty Liver / Q000235:genetics*; D005247:Feeding Behavior / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D005943:Gluconeogenesis / Q000235:genetics / Q000502:physiology; D007113:Immunity, Innate / Q000235:genetics*; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013493:Suprachiasmatic Nucleus / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D001391:Azo Compounds; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D009687:Nuclear Proteins; D014157:Transcription Factors; C102804:nocturnin; C011049:oil red O