Rocío Del M Saavedra-Peña, Natalia Taylor, Matthew S Rodeheffer
{"title":"Insights of the role of estrogen in obesity from two models of ERα deletion.","authors":"Rocío Del M Saavedra-Peña, Natalia Taylor, Matthew S Rodeheffer","doi":"10.1530/JME-21-0260","DOIUrl":null,"url":null,"abstract":"<p><p>Sex hormones play a pivotal role in physiology and disease. Estrogen, the female sex hormone, has been long implicated in having protective roles against obesity. However, the direct impact of estrogens in white adipose tissue (WAT) function and growth is not understood. Here, we show that the deletion of estrogen receptor alpha (ERα; Esr1) from adipocytes using Adipoq-credoes not affect adipose mass in male or female mice under normal or high-fat diet (HFD) conditions. However, loss of ERα in adipocyte precursor cells (APs) via Pdgfra-cre leads to exacerbated obesity upon HFD feeding in both male and female mice, with s.c. adipose (SWAT)-specific expansion in male mice. Further characterization of these mice revealed infertility and increased plasma levels of sex hormones, including estradiol in female mice and androgens in male mice. These findings compromise the study of estrogen signaling within the adipocyte lineage using the Pdgfra-crestrain. However, AP transplant studies demonstrate that the increased AP hyperplasia in male SWAT upon Pdgfra-cre-mediated ablation of ERα is not driven by AP-intrinsic mechanisms but is rather mediated by off-target effects. These data highlight the inherent difficulties in studying models that disrupt the intricate balance of sex hormones. Thus, better approaches are needed to study the cellular and molecular mechanisms of sex hormones in obesity and disease.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"68 4","pages":"179-194"},"PeriodicalIF":3.6000,"publicationDate":"2022-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10173145/pdf/nihms-1887822.pdf","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of molecular endocrinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1530/JME-21-0260","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 1
Abstract
Sex hormones play a pivotal role in physiology and disease. Estrogen, the female sex hormone, has been long implicated in having protective roles against obesity. However, the direct impact of estrogens in white adipose tissue (WAT) function and growth is not understood. Here, we show that the deletion of estrogen receptor alpha (ERα; Esr1) from adipocytes using Adipoq-credoes not affect adipose mass in male or female mice under normal or high-fat diet (HFD) conditions. However, loss of ERα in adipocyte precursor cells (APs) via Pdgfra-cre leads to exacerbated obesity upon HFD feeding in both male and female mice, with s.c. adipose (SWAT)-specific expansion in male mice. Further characterization of these mice revealed infertility and increased plasma levels of sex hormones, including estradiol in female mice and androgens in male mice. These findings compromise the study of estrogen signaling within the adipocyte lineage using the Pdgfra-crestrain. However, AP transplant studies demonstrate that the increased AP hyperplasia in male SWAT upon Pdgfra-cre-mediated ablation of ERα is not driven by AP-intrinsic mechanisms but is rather mediated by off-target effects. These data highlight the inherent difficulties in studying models that disrupt the intricate balance of sex hormones. Thus, better approaches are needed to study the cellular and molecular mechanisms of sex hormones in obesity and disease.
期刊介绍:
The Journal of Molecular Endocrinology is an official journal of the Society for Endocrinology and is endorsed by the European Society of Endocrinology and the Endocrine Society of Australia.
Journal of Molecular Endocrinology is a leading global journal that publishes original research articles and reviews. The journal focuses on molecular and cellular mechanisms in endocrinology, including: gene regulation, cell biology, signalling, mutations, transgenics, hormone-dependant cancers, nuclear receptors, and omics. Basic and pathophysiological studies at the molecule and cell level are considered, as well as human sample studies where this is the experimental model of choice. Technique studies including CRISPR or gene editing are also encouraged.