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

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

doi:10.1016/j.molmet.2014.05.007

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

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

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

Abstract

Hypoxia Inducible Factor 1 (HIF-1) promotes fibrosis and inflammation in adipose tissues, while estrogens and Estrogen Receptor α (ERα) 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-1α is ubiquitinated following 17-β estradiol (E2)/ERα mediated Phd3 transcription. Manipulating ERα 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/ERα, PHD3 and HIF-1 in adipose tissues, providing a mechanistic explanation for the protective effect of E2/ERα in adipose tissue.

Original language	English (US)
Pages (from-to)	642-651
Number of pages	10
Journal	Molecular Metabolism
Volume	3
Issue number	6
DOIs	https://doi.org/10.1016/j.molmet.2014.05.007
State	Published - Sep 2014

Keywords

Adipose tissue
Estrogen
Fibrosis
Inflammation
Metabolic syndrome
Obesity

ASJC Scopus subject areas

Molecular Biology
Cell Biology

Access to Document

10.1016/j.molmet.2014.05.007

Cite this

@article{8cacdd7412b44c35bcb353f046c497d7,

title = "ERα upregulates Phd3 to ameliorate HIF-1 induced fibrosis and inflammation in adipose tissue",

abstract = "Hypoxia Inducible Factor 1 (HIF-1) promotes fibrosis and inflammation in adipose tissues, while estrogens and Estrogen Receptor α (ERα) 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-1α is ubiquitinated following 17-β estradiol (E2)/ERα mediated Phd3 transcription. Manipulating ERα 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/ERα, PHD3 and HIF-1 in adipose tissues, providing a mechanistic explanation for the protective effect of E2/ERα in adipose tissue.",

keywords = "Adipose tissue, Estrogen, Fibrosis, Inflammation, Metabolic syndrome, Obesity",

author = "Min Kim and Neinast, {Michael D.} and Frank, {Aaron P.} and Kai Sun and Jiyoung Park and Zehr, {Jordan A.} and Lavanya Vishvanath and Eugenia Morselli and Mason Amelotte and Palmer, {Biff F} and Gupta, {Rana K} and Scherer, {Philipp E} and Clegg, {Deborah J.}",

year = "2014",

month = sep,

doi = "10.1016/j.molmet.2014.05.007",

language = "English (US)",

volume = "3",

pages = "642--651",

journal = "Molecular Metabolism",

issn = "2212-8778",

publisher = "Elsevier GmbH",

number = "6",

}

TY - JOUR

T1 - ERα upregulates Phd3 to ameliorate HIF-1 induced fibrosis and inflammation in adipose tissue

AU - Kim, Min

AU - Neinast, Michael D.

AU - Frank, Aaron P.

AU - Sun, Kai

AU - Park, Jiyoung

AU - Zehr, Jordan A.

AU - Vishvanath, Lavanya

AU - Morselli, Eugenia

AU - Amelotte, Mason

AU - Palmer, Biff F

AU - Gupta, Rana K

AU - Scherer, Philipp E

AU - Clegg, Deborah J.

PY - 2014/9

Y1 - 2014/9

N2 - Hypoxia Inducible Factor 1 (HIF-1) promotes fibrosis and inflammation in adipose tissues, while estrogens and Estrogen Receptor α (ERα) 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-1α is ubiquitinated following 17-β estradiol (E2)/ERα mediated Phd3 transcription. Manipulating ERα 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/ERα, PHD3 and HIF-1 in adipose tissues, providing a mechanistic explanation for the protective effect of E2/ERα in adipose tissue.

AB - Hypoxia Inducible Factor 1 (HIF-1) promotes fibrosis and inflammation in adipose tissues, while estrogens and Estrogen Receptor α (ERα) 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-1α is ubiquitinated following 17-β estradiol (E2)/ERα mediated Phd3 transcription. Manipulating ERα 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/ERα, PHD3 and HIF-1 in adipose tissues, providing a mechanistic explanation for the protective effect of E2/ERα in adipose tissue.

KW - Adipose tissue

KW - Estrogen

KW - Fibrosis

KW - Inflammation

KW - Metabolic syndrome

KW - Obesity

UR - http://www.scopus.com/inward/record.url?scp=84906239136&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84906239136&partnerID=8YFLogxK

U2 - 10.1016/j.molmet.2014.05.007

DO - 10.1016/j.molmet.2014.05.007

M3 - Article

C2 - 25161887

AN - SCOPUS:84906239136

SN - 2212-8778

VL - 3

SP - 642

EP - 651

JO - Molecular Metabolism

JF - Molecular Metabolism

IS - 6

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this