High-fat diet and estrogen impacts the colon and its transcriptome in a sex-dependent manner
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 estroge...
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| Veröffentlicht in: | Scientific reports 2020-09, Vol.10 (1), p.16160, Article 16160 |
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| description | 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. |
| doi_str_mv | 10.1038/s41598-020-73166-1 |
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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. 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We here demonstrate how HFD and estrogens modulate the colon microenvironment in a sex- and ER-specific manner.</description><subject>631/443/319</subject><subject>631/80</subject><subject>692/420/256/2515</subject><subject>692/499</subject><subject>692/699/1503</subject><subject>692/700/2814</subject><subject>Animals</subject><subject>Blood Glucose - metabolism</subject><subject>Body weight</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Colon - drug effects</subject><subject>Colon - metabolism</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Diet</subject><subject>Diet, High-Fat</subject><subject>Epithelial cells</subject><subject>Estradiol - pharmacology</subject><subject>Estrogen Receptor beta - agonists</subject><subject>Estrogen receptors</subject><subject>Estrogens</subject><subject>Female</subject><subject>Gender differences</subject><subject>Gene expression</subject><subject>Gene Expression - 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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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32999402</pmid><doi>10.1038/s41598-020-73166-1</doi><oa>free_for_read</oa></addata></record> |
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| subjects | 631/443/319 631/80 692/420/256/2515 692/499 692/699/1503 692/700/2814 Animals Blood Glucose - metabolism Body weight Cell proliferation Cell Proliferation - drug effects Colon - drug effects Colon - metabolism Colorectal cancer Colorectal carcinoma Diet Diet, High-Fat Epithelial cells Estradiol - pharmacology Estrogen Receptor beta - agonists Estrogen receptors Estrogens Female Gender differences Gene expression Gene Expression - drug effects High fat diet Humanities and Social Sciences Infiltration Macrophages Male Medicin och hälsovetenskap Metabolic disorders Metabolic syndrome Mice multidisciplinary Nitriles - pharmacology Obesity - metabolism Science Science (multidisciplinary) Sex Sex differences Sex Factors Transcription activation Transcriptome - drug effects Xenoestrogens |
| title | High-fat diet and estrogen impacts the colon and its transcriptome in a sex-dependent manner |
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