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^*

^*Autor correspondiente de este trabajo

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

46 Citas (Scopus)

Resumen

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.

Idioma original	Inglés
Páginas (desde-hasta)	642-651
Número de páginas	10
Publicación	Molecular Metabolism
Volumen	3
N.º	6
DOI	https://doi.org/10.1016/j.molmet.2014.05.007
Estado	Publicada - 2014
Publicado de forma externa	Sí

Áreas temáticas de ASJC Scopus

Biología molecular
Biología celular

ODS de las Naciones Unidas

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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",

volume = "3",

pages = "642--651",

journal = "Molecular Metabolism",

issn = "2212-8778",

publisher = "Elsevier GmbH",

number = "6",

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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

U2 - 10.1016/j.molmet.2014.05.007

DO - 10.1016/j.molmet.2014.05.007

M3 - Article

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

Resumen

Áreas temáticas de ASJC Scopus

ODS de las Naciones Unidas

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