ER alpha upregulates Phd3 to ameliorate HIF-1 induced fibrosis and inflammation in adipose tissue

作者：Kim Min; Neinast Michael D; Frank Aaron P; Sun Kai; Park Jiyoung; Zehr Jordan A; Vishvanath Lavanya; Morselli Eugenia; Amelotte Mason; Palmer Biff F; Gupta Rana K; Scherer Philipp E; Clegg Deborah J^*

来源：Molecular Metabolism, 2014, 3(6): 642-651.

DOI：10.1016/j.molmet.2014.05.007

• Obesity
• Metabolic syndrome
• Estrogen
• Adipose tissue
• Fibrosis
• Inflammation

Hypoxia Inducible Factor 1 (HIF-1) promotes fibrosis and inflammation in adipose tissues, while estrogens and Estrogen Receptor alpha (ER alpha) have the opposite effect. Here we identify an Estrogen Response Element (ERE) in the promoter of Phd3, which is a negative regulatory enzyme of HIF-1, and we demonstrate HIF-1 alpha is ubiquitinated following 17-beta estradiol (E2)/ER alpha mediated Phd3 transcription. Manipulating ERa in vivo increases Phd3 transcription and reduces HIF-1 activity, while addition of PHD3 ameliorates adipose tissue fibrosis and inflammation. Our findings outline a novel regulatory relationship between E2/ER alpha, PHD3 and HIF-1 in adipose tissues, providing a mechanistic explanation for the protective effect of E2/ER alpha in adipose tissue.

• 出版日期2014-9