Nocturnin regulates circadian trafficking of dietary lipid in intestinal enterocytes

Nicholas Douris, Shihoko Kojima, Xiaoyue Pan, Alexandra F. Lerch-Gaggl, Son Q. Duong, M. Mahmood Hussain, Carla B. Green

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Background: Efficient metabolic function in mammals depends on the circadian clock, which drives temporal regulation of metabolic processes. Nocturnin is a clock-regulated deadenylase that controls its target mRNA expression posttranscriptionally through poly(A) tail removal. Mice lacking nocturnin (Noc -/- mice) are resistant to diet-induced obesity and hepatic steatosis yet are not hyperactive or hypophagic. Results: Here we show that nocturnin is expressed rhythmically in the small intestine and is induced by olive oil gavage and that the Noc -/- mice have reduced chylomicron transit into the plasma following the ingestion of dietary lipids. Genes involved in triglyceride synthesis and storage and chylomicron formation have altered expression, and large cytoplasmic lipid droplets accumulate in the apical domains of the Noc -/- enterocytes. The physiological significance of this deficit in absorption is clear because maintenance of Noc -/- mice on diets that challenge the chylomicron synthesis pathway result in significant reductions in body weight, whereas diets that bypass this pathway do not. Conclusions: Therefore, we propose that nocturnin plays an important role in the trafficking of dietary lipid in the intestinal enterocytes by optimizing efficient absorption of lipids.

Original languageEnglish (US)
Pages (from-to)1347-1355
Number of pages9
JournalCurrent Biology
Volume21
Issue number16
DOIs
StatePublished - Aug 23 2011

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Douris, N., Kojima, S., Pan, X., Lerch-Gaggl, A. F., Duong, S. Q., Hussain, M. M., & Green, C. B. (2011). Nocturnin regulates circadian trafficking of dietary lipid in intestinal enterocytes. Current Biology, 21(16), 1347-1355. https://doi.org/10.1016/j.cub.2011.07.018