High-fat diet and estrogen impacts the colon and its transcriptome in a sex-dependent manner

Sci Rep. 2020 Sep 30;10(1):16160. doi: 10.1038/s41598-020-73166-1.


There is a strong association between obesity and colorectal cancer (CRC), especially in men, whereas estrogen protects against both the metabolic syndrome and CRC. Colon is the first organ to respond to high-fat diet (HFD), and estrogen receptor beta (ERβ) can attenuate CRC development. How estrogen impacts the colon under HFD and related sex differences has, however, not been investigated. To dissect this, mice were fed control diet or HFD for 13 weeks and administered receptor-selective estrogenic ligands for the last three weeks. We recorded impact on metabolism, colon crypt proliferation, macrophage infiltration, and the colon transcriptome. We found clear sex differences in the colon transcriptome and in the impact by HFD and estrogens, including on clock genes. ERα-selective activation reduced body weight and generated systemic effects, whereas ERβ-selective activation had local effects in the colon, attenuating HFD-induced macrophage infiltration and epithelial cell proliferation. We here demonstrate how HFD and estrogens modulate the colon microenvironment in a sex- and ER-specific manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Cell Proliferation / drug effects
  • Colon / drug effects
  • Colon / metabolism*
  • Diet, High-Fat*
  • Estradiol / pharmacology*
  • Estrogen Receptor beta / agonists*
  • Female
  • Gene Expression / drug effects
  • Male
  • Mice
  • Nitriles / pharmacology
  • Obesity / metabolism*
  • Sex Factors
  • Transcriptome / drug effects*


  • 2,3-bis(4-hydroxyphenyl)-propionitrile
  • Blood Glucose
  • Estrogen Receptor beta
  • Nitriles
  • Estradiol