17α-estradiol alleviates age-related metabolic and inflammatory dysfunction in male mice without inducing feminization

Stout, Michael B. , Steyn, Frederik J. , Jurczak, Michael J. , Camporez, Joao-Paulo G., Zhu, Yi , Hawse, John R., Jurk, Diana, Palmer, Allyson K. , Xu, Ming, Pirtskhalava, Tamar, Evans, Glenda L., De Souza Santos, Roberta, Frank, Aaron P. , White, Thomas A., Monroe, David G. , Singh, Ravinder J., Casaclang-Verzosa, Grace, Miller, Jordan D. , Clegg, Deborah J., LeBrasseur, Nathan K., Von Zglinicki, Thomas, Shulman, Gerald I. , Tchkonia, Tamara and Kirkland, James L. (2017) 17α-estradiol alleviates age-related metabolic and inflammatory dysfunction in male mice without inducing feminization. Journals of Gerontology, Series A, 72 1: 3-15. doi:10.1093/gerona/glv309


Author Stout, Michael B. 
Steyn, Frederik J. 
Jurczak, Michael J. 
Camporez, Joao-Paulo G.
Zhu, Yi 
Hawse, John R.
Jurk, Diana
Palmer, Allyson K. 
Xu, Ming
Pirtskhalava, Tamar
Evans, Glenda L.
De Souza Santos, Roberta
Frank, Aaron P. 
White, Thomas A.
Monroe, David G. 
Singh, Ravinder J.
Casaclang-Verzosa, Grace
Miller, Jordan D. 
Clegg, Deborah J.
LeBrasseur, Nathan K.
Von Zglinicki, Thomas
Shulman, Gerald I. 
Tchkonia, Tamara
Kirkland, James L.
Title 17α-estradiol alleviates age-related metabolic and inflammatory dysfunction in male mice without inducing feminization
Journal name Journals of Gerontology, Series A   Check publisher's open access policy
ISSN 1758-535X
1079-5006
Publication date 2017-01-01
Year available 2016
Sub-type Article (original research)
DOI 10.1093/gerona/glv309
Open Access Status Not yet assessed
Volume 72
Issue 1
Start page 3
End page 15
Total pages 13
Place of publication Cary, NC, United States
Publisher Oxford University Press
Collection year 2018
Language eng
Abstract Aging is associated with visceral adiposity, metabolic disorders, and chronic low-grade inflammation. 17α-estradiol (17α-E2), a naturally occurring enantiomer of 17α-estradiol (17α-E2), extends life span in male mice through unresolved mechanisms. We tested whether 17α-E2 could alleviate age-related metabolic dysfunction and inflammation. 17α-E2 reduced body mass, visceral adiposity, and ectopic lipid deposition without decreasing lean mass. These declines were associated with reductions in energy intake due to the activation of hypothalamic anorexigenic pathways and direct effects of 17α-E2 on nutrient-sensing pathways in visceral adipose tissue. 17α-E2 did not alter energy expenditure or excretion. Fasting glucose, insulin, and glycosylated hemoglobin were also reduced by 17α-E2, and hyperinsulinemic-euglycemic clamps revealed improvements in peripheral glucose disposal and hepatic glucose production. Inflammatory mediators in visceral adipose tissue and the circulation were reduced by 17α-E2. 17α-E2 increased AMPK? and reduced mTOR complex 1 activity in visceral adipose tissue but not in liver or quadriceps muscle, which is in contrast to the generalized systemic effects of caloric restriction. These beneficial phenotypic changes occurred in the absence of feminization or cardiac dysfunction, two commonly observed deleterious effects of exogenous estrogen administration. Thus, 17α-E2 holds potential as a novel therapeutic for alleviating age-related metabolic dysfunction through tissue-specific effects.
Keyword 17α-Estradiol
Adipose tissue
Hypothalamus
Inflammation
Metabolism
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
HERDC Pre-Audit
School of Biological Sciences Publications
 
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