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PMID:24567372

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Citation

Ihunnah, CA, Wada, T, Philips, BJ, Ravuri, SK, Gibbs, RB, Kirisci, L, Rubin, JP, Marra, KG and Xie, W' (2014) Estrogen Sulfotransferase (EST/SULT1E1) Promotes Human Adipogenesis. Mol. Cell. Biol. '

Abstract

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 subcutaneous 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 γ (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.

Links

PubMed Online version:10.1128/MCB.01147-13

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:ST1E1

GO:0045600: positive regulation of fat cell differentiation

ECO:0000315:

P

Figure 2A and 2C show that preadipocytes in which SULT1E1 mRNA was overexpressed had higher rates of adipogenesis than the control preadipocytes with low levels of SULT1E1.

complete
CACAO 9971

HUMAN:ST1E1

involved_in

GO:0045600: positive regulation of fat cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

See also

References

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