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GSE149811: Estrogen signaling modulates the colon microenvironment during obesity

Bulk RNA sequencing

Epidemiological studies highlight a strong association between obesity and colorectal cancer (CRC). This association appears stronger in men and a role for sex hormones is indicated by epidemiological studies. Especially estrogen is protective against CRC and correlated to several aspects of the metabolic syndrome. Anti-inflammatory and anti-tumorigenic effects of estrogen in colon have been demonstrated to act via estrogen receptor beta (ER). This led us to hypothesize that estrogenic signaling, through both systemic and local effects might modulate the colon microenvironment during HFD-induced obesity. In order to test our hypothesis mice were fed a control diet or a high fat diet (HFD) for 3 weeks and treated with different estrogenic ligands. In the present study, we demonstrate that there are sex-differences in the response to HFD-induced obesity and in the colon transcriptome. Both sexes develop obesity with an impaired circadian rhythm but the male metabolic profile is more sensitive to HFD and increased the colon epithelial cell proliferation. Females were resistant to impaired glucose metabolism, but HFD-feeding increased the infiltration of macrophages. Estrogen signaling in males, via ER, presented anti-obesogenic effects. However, systemic and/or local activation of both ER and ER restored the circadian rhythm in the males. In females, systemic activation of ER restored the circadian rhythm, however, systemic and/or local activation of ER down-regulated the expression of macrophage markers. These results suggest that estrogen signaling through systemic and/or local activation of ER can regulate the colon microenvironment during HFD-induced obesity. SOURCE: Cecilia Williams (cecilia.williams@scilifelab.se) - Karolinska Institute

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