Document Type
Article
Abstract
Context
We created an innovative mouse model that enables inducible overexpression of estrogen receptor-alpha (ERα), specifically in adipose tissue (Adipo-ERα↑). Objective
We aimed to investigate how elevated Adipo-ERα↑ influences the development of high-fat diet (HFD)-induced obesity in both male and female mice. Methods
Male and female Adipo-ERα↑ mice and littermate controls were fed a low-fat diet (LFD) or HFD for 13 weeks. Adipo-ERα↑ was induced at the initiation of dietary treatment. Body morphology and composition, hepatic lipid accumulation, glucose tolerance, fasting insulin concentrations, and adipose tissue mRNA profiling were assessed. Liquid chromatography–mass spectrometry was used to determine circulating and adipose tissue sex steroid content. Results
Adipo-ERα↑ significantly reduced adiposity and hepatic lipid accumulation in HFD-fed female mice but not in male mice. However, in both sexes, Adipo-ERα↑ greatly reduced adipose tissue inflammation characteristic of obesity. Despite these effects, Adipo-ERα↑ did not improve glucose tolerance or fasting insulin levels and did not affect circulating and adipose tissue sex steroid content. Conclusion
Adipo-ERα↑ elicits distinct sex-specific effects with respect to body composition and hepatic lipid accumulation, which are likely driven by variations in circulating and tissue estrogen levels. Nonetheless, despite differences in estrogen levels, Adipo-ERα↑ profoundly reduced obesity-linked adipose tissue inflammation in both sexes, providing further evidence that therapeutically targeting ERα may be beneficial for treating obesity-associated inflammation.
Digital Object Identifier (DOI)
Publication Info
Published in Journal of the Endocrine Society, Volume 9, Issue 10, 2025.
Rights
© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. See the journal About page for additional terms.
APA Citation
Hope, M. C., Unger, C. A., Kettering, M. C., Socia, C. E., Aladhami, A. K., Rice, B. C., Niamira, D. S., Wiznitzer, B. P., Altomare, D., Cotham, W. E., & Enos, R. T. (2025). Adipose Tissue Estrogen Receptor-Alpha Overexpression Ameliorates High-Fat Diet–Induced Adipose Tissue Inflammation. Journal of the Endocrine Society, 9(10). https://doi.org/10.1210/jendso/bvaf134