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

Carla B. Green, Nicholas Douris, Shihoko Kojima, Carl A. Strayer, Joseph Fogerty, David Lourim, Susanna R. Keller, Joseph C. Besharse

Research output: Contribution to journalArticlepeer-review

158 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)9888-9893
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number23
DOIs
StatePublished - Jun 5 2007

Keywords

  • Clock
  • Diabetes
  • Lipid
  • Posttranscriptional
  • mRNA

ASJC Scopus subject areas

  • General

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