Serotonin transporter deficiency drives estrogen-dependent obesity and glucose intolerance

Abstract Depression and use of antidepressant medications are both associated with increased risk of obesity, potentially attributed to a reduced serotonin transporter (SERT) function. However, how SERT deficiency promotes obesity is unknown. Here, we demonstrated that SERT −/− mice display abnormal...

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Autores principales:	Weibin Zha, Horace T. B. Ho, Tao Hu, Mary F. Hebert, Joanne Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/76530317f3e348398465b60bfd95a71c
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spelling	oai:doaj.org-article:76530317f3e348398465b60bfd95a71c2021-12-02T16:08:00ZSerotonin transporter deficiency drives estrogen-dependent obesity and glucose intolerance10.1038/s41598-017-01291-52045-2322https://doaj.org/article/76530317f3e348398465b60bfd95a71c2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01291-5https://doaj.org/toc/2045-2322Abstract Depression and use of antidepressant medications are both associated with increased risk of obesity, potentially attributed to a reduced serotonin transporter (SERT) function. However, how SERT deficiency promotes obesity is unknown. Here, we demonstrated that SERT −/− mice display abnormal fat accumulation in both white and brown adipose tissues, glucose intolerance and insulin resistance while exhibiting suppressed aromatase (Cyp19a1) expression and reduced circulating 17β-estradiol levels. 17β-estradiol replacement in SERT −/− mice reversed the obesity and glucose intolerance, supporting a role for estrogen in SERT deficiency-associated obesity and glucose intolerance. Treatment of wild type mice with paroxetine, a chemical inhibitor of SERT, also resulted in Cyp19a1 suppression, decreased circulating 17β-estradiol levels, abnormal fat accumulation, and glucose intolerance. Such effects were not observed in paroxetine-treated SERT −/− mice. Conversely, pregnant SERT −/− mice displayed normalized estrogen levels, markedly reduced fat accumulation, and improved glucose tolerance, which can be eliminated by an antagonist of estrogen receptor α (ERα). Together, these findings support that estrogen suppression is involved in SERT deficiency-induced obesity and glucose intolerance, and suggest approaches to restore 17β-estradiol levels as a novel treatment option for SERT deficiency associated obesity and metabolic abnormalities.Weibin ZhaHorace T. B. HoTao HuMary F. HebertJoanne WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Weibin Zha Horace T. B. Ho Tao Hu Mary F. Hebert Joanne Wang Serotonin transporter deficiency drives estrogen-dependent obesity and glucose intolerance
description	Abstract Depression and use of antidepressant medications are both associated with increased risk of obesity, potentially attributed to a reduced serotonin transporter (SERT) function. However, how SERT deficiency promotes obesity is unknown. Here, we demonstrated that SERT −/− mice display abnormal fat accumulation in both white and brown adipose tissues, glucose intolerance and insulin resistance while exhibiting suppressed aromatase (Cyp19a1) expression and reduced circulating 17β-estradiol levels. 17β-estradiol replacement in SERT −/− mice reversed the obesity and glucose intolerance, supporting a role for estrogen in SERT deficiency-associated obesity and glucose intolerance. Treatment of wild type mice with paroxetine, a chemical inhibitor of SERT, also resulted in Cyp19a1 suppression, decreased circulating 17β-estradiol levels, abnormal fat accumulation, and glucose intolerance. Such effects were not observed in paroxetine-treated SERT −/− mice. Conversely, pregnant SERT −/− mice displayed normalized estrogen levels, markedly reduced fat accumulation, and improved glucose tolerance, which can be eliminated by an antagonist of estrogen receptor α (ERα). Together, these findings support that estrogen suppression is involved in SERT deficiency-induced obesity and glucose intolerance, and suggest approaches to restore 17β-estradiol levels as a novel treatment option for SERT deficiency associated obesity and metabolic abnormalities.
format	article
author	Weibin Zha Horace T. B. Ho Tao Hu Mary F. Hebert Joanne Wang
author_facet	Weibin Zha Horace T. B. Ho Tao Hu Mary F. Hebert Joanne Wang
author_sort	Weibin Zha
title	Serotonin transporter deficiency drives estrogen-dependent obesity and glucose intolerance
title_short	Serotonin transporter deficiency drives estrogen-dependent obesity and glucose intolerance
title_full	Serotonin transporter deficiency drives estrogen-dependent obesity and glucose intolerance
title_fullStr	Serotonin transporter deficiency drives estrogen-dependent obesity and glucose intolerance
title_full_unstemmed	Serotonin transporter deficiency drives estrogen-dependent obesity and glucose intolerance
title_sort	serotonin transporter deficiency drives estrogen-dependent obesity and glucose intolerance
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/76530317f3e348398465b60bfd95a71c
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_version_	1718384663467130880

Serotonin transporter deficiency drives estrogen-dependent obesity and glucose intolerance

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