Regulation of Body Composition by the Microbiota and the Circadian Clock

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. In this dissertation, I show that the microbiota regulates body composition through the circadian transcription factor NFIL3 in intestinal epithelial cells. First, epithelial NFIL3 promotes lipid absorption and export in the intestine by regulating a circadian expression program of epithelial lipid metabolic genes. Second, 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. 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.