Nocturnin Regulates Circadian Trafficking of Dietary Lipid in Intestinal Enterocytes

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 post-transcriptionally 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.