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.