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Estrogen sulfotransferase(est/sult1e1) promotes human adipogenesis (LB606)
Author(s) -
Ihunnah Chibueze,
Philips Brian,
Ravuri Sudheer,
Gibbs Robert,
Kirisci Levent,
Rubin J,
Marra Kacey,
Xie Wen
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb606
Subject(s) - adipogenesis , gene knockdown , estrogen , medicine , endocrinology , adipose tissue , estrogen receptor , aromatase , chemistry , peroxisome proliferator activated receptor , biology , receptor , gene , biochemistry , cancer , breast cancer
The estrogen sulfotransferase (EST/SULT1E1) is known to catalyze the sulfoconjugation and deactivation of estrogens. The goal of this study is to determine whether and how EST plays a role in human adipogenesis. By using human primary adipose derived stem cells (ASCs) and whole fat tissues from the abdominal fat of obese and non‐obese subjects, we showed that the expression of EST was low in pre‐adipocytes but increased upon differentiation. Overexpression and knockdown of EST in ASCs promoted and inhibited differentiation, respectively. The pro‐adipogenic activity of EST in humans was opposite to the anti‐adipogenic effect of the same enzyme in rodents. Mechanistically, EST promoted adipogenesis by deactivating estrogens. The pro‐adipogenic effect of EST can be recapitulated by using an estrogen receptor (ER) antagonist or ERα knockdown. In contrast, activation of ER in ASCs inhibited adipogenesis by decreasing the recruitment of the adipogenic peroxisome proliferator activated receptor(PPARγ) onto its target gene promoters, whereas ER antagonism increased the recruitment of PPARγ to its target gene promoters. Linear regression analysis revealed a positive correlation between the expression of EST and body mass index (BMI)as well as a negative correlation between the ERα expression and BMI. We conclude that EST is a pro‐adipogenic factor, which may serve as a druggable target to inhibit the turnover and accumulation of adipocytes in obese patients. Grant Funding Source : Supported by NIH Ruth L. Kirschstein National Research Service Awards for Individual Predoctoral Fellowships to Promote Diversity in Health‐Related Research