Metabolism, the microbiome, and the circadian clock

Abstract

The intestinal microbiota has been identified as an environmental factor that markedly impacts energy storage and body fat accumulation, yet the underlying mechanisms remain unclear. We have shown that the microbiota regulates body composition through the circadian transcription factor NFIL3. Nfil3 transcription oscillates diurnally in intestinal epithelial cells and the amplitude of the circadian oscillation is controlled by the microbiota through group 3 innate lymphoid cells (ILC3), STAT3, and the epithelial cell circadian clock. NFIL3 controls expression of a circadian lipid metabolic program and regulates lipid absorption and export in intestinal epithelial cells. These findings provide mechanistic insight into how the intestinal microbiota regulates body composition and establish NFIL3 as an essential molecular link among the microbiota, the circadian clock, and host metabolism.Support or Funding InformationNIH grant R01 DK070855 (L.V.H.); Burroughs Wellcome Foundation Investigators in the Pathogenesis of Infectious Diseases Award (L.V.H.); the Welch Foundation (L.V.H.), and the Howard Hughes Medical Institute (L.V.H.)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.