A dietary change to a high-fat diet initiates a rapid adaptation of the intestine

Long-term impacts of diet have been well studied; however, the immediate response of the intestinal epithelium to a change in nutrients remains poorly understood. We use physiological metrics and single-cell transcriptomics to interrogate the intestinal epithelial cell response to a high-fat diet (HFD). Within 1 day of HFD exposure, mice exhibit altered whole-body physiology and increased intestinal epithelial proliferation. Single-cell transcriptional analysis on day 1 reveals a cell- stress response in intestinal crypts and a shift toward fatty acid metabolism. By 3 days of HFD, computational trajectory analysis suggests an emergence of progenitors, with a transcriptional profile shifting from secretory populations toward enterocytes. Furthermore, enterocytes upregulate lipid absorption genes and show increased lipid absorption in vivo over 7 days of HFD. These findings demonstrate the rapid intestinal epithelial response to a dietary change and help illustrate the essential ability of animals to adapt to shifting nutritional environments.

Automated summary

This study investigates the immediate response of the intestinal epithelium to a high-fat diet using physiological metrics and single-cell transcriptomics. The findings indicate that mice exhibit altered whole-body physiology and increased intestinal epithelial proliferation within one day of high-fat diet exposure. Furthermore, the study reveals a shift towards fatty acid metabolism and an emergence of progenitor cells in response to the high-fat diet.