SGLT2 Inhibitor-Induced Sympathoexcitation in White Adipose Tissue: A Novel Mechanism for Beiging

Recent preclinical data show that sodium glucose cotransporter 2 (SGLT2) inhibitors are able to reduce weight gain and induce beiging in white adipose tissue (WAT). We have previously shown that in neurogenic hypertensive Schlager (BPH/2J) mice, treatment with the SGLT2 inhibitor, Dapagliflozin, red...

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Main Authors: Jennifer R. Matthews, Lakshini Y. Herat, Aaron L. Magno, Shelley Gorman, Markus P. Schlaich, Vance B. Matthews
Format: Article
Language:English
Published: MDPI AG 2020-11-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/8/11/514
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spelling doaj-b32a940e338e4219be8aa309f5bc05d32020-11-25T04:01:45ZengMDPI AGBiomedicines2227-90592020-11-01851451410.3390/biomedicines8110514SGLT2 Inhibitor-Induced Sympathoexcitation in White Adipose Tissue: A Novel Mechanism for BeigingJennifer R. Matthews0Lakshini Y. Herat1Aaron L. Magno2Shelley Gorman3Markus P. Schlaich4Vance B. Matthews5Dobney Hypertension Centre, School of Biomedical Science—Royal Perth Hospital Unit, University of Western Australia, Crawley, WA 6009, AustraliaDobney Hypertension Centre, School of Biomedical Science—Royal Perth Hospital Unit, University of Western Australia, Crawley, WA 6009, AustraliaResearch Centre, Royal Perth Hospital, Perth, WA 6000, AustraliaTelethon Kids Institute, University of Western Australia, Perth, WA 6009, AustraliaDobney Hypertension Centre, School of Medicine—Royal Perth Hospital Unit, University of Western Australia, Crawley, WA 6009, AustraliaDobney Hypertension Centre, School of Biomedical Science—Royal Perth Hospital Unit, University of Western Australia, Crawley, WA 6009, AustraliaRecent preclinical data show that sodium glucose cotransporter 2 (SGLT2) inhibitors are able to reduce weight gain and induce beiging in white adipose tissue (WAT). We have previously shown that in neurogenic hypertensive Schlager (BPH/2J) mice, treatment with the SGLT2 inhibitor, Dapagliflozin, reduced blood pressure and prevented weight gain. Here we show that chemical sympathetic denervation achieved by systemic administration of 6-hydroxy-dopamine (6-OHDA) reduces body weight and the heightened sympathetic nervous system (SNS) innervation in WAT. Furthermore, we demonstrate that 2 weeks of Dapagliflozin treatment increases SNS innervation in WAT of hypertensive mice. This increase is accompanied by a non-significant elevation in mRNA levels of the <i>Ucp1</i> and <i>Pgc-1α</i> genes, which are markers of beiging. No significant difference in the mRNA levels of the inflammatory mediators <i>Il-6</i> and <i>Tnf-α</i> were detected in WAT of Dapagliflozin treated mice. These findings suggest that SGLT-2 inhibitor-associated prevention of weight gain may be mediated, at least in part, by inducing the beiging of WAT.https://www.mdpi.com/2227-9059/8/11/514sympathetic nervous systemsodium glucose cotransporter 2 inhibitionDapagliflozinbeigingadipose tissuehypertension
collection DOAJ
language English
format Article
sources DOAJ
author Jennifer R. Matthews
Lakshini Y. Herat
Aaron L. Magno
Shelley Gorman
Markus P. Schlaich
Vance B. Matthews
spellingShingle Jennifer R. Matthews
Lakshini Y. Herat
Aaron L. Magno
Shelley Gorman
Markus P. Schlaich
Vance B. Matthews
SGLT2 Inhibitor-Induced Sympathoexcitation in White Adipose Tissue: A Novel Mechanism for Beiging
Biomedicines
sympathetic nervous system
sodium glucose cotransporter 2 inhibition
Dapagliflozin
beiging
adipose tissue
hypertension
author_facet Jennifer R. Matthews
Lakshini Y. Herat
Aaron L. Magno
Shelley Gorman
Markus P. Schlaich
Vance B. Matthews
author_sort Jennifer R. Matthews
title SGLT2 Inhibitor-Induced Sympathoexcitation in White Adipose Tissue: A Novel Mechanism for Beiging
title_short SGLT2 Inhibitor-Induced Sympathoexcitation in White Adipose Tissue: A Novel Mechanism for Beiging
title_full SGLT2 Inhibitor-Induced Sympathoexcitation in White Adipose Tissue: A Novel Mechanism for Beiging
title_fullStr SGLT2 Inhibitor-Induced Sympathoexcitation in White Adipose Tissue: A Novel Mechanism for Beiging
title_full_unstemmed SGLT2 Inhibitor-Induced Sympathoexcitation in White Adipose Tissue: A Novel Mechanism for Beiging
title_sort sglt2 inhibitor-induced sympathoexcitation in white adipose tissue: a novel mechanism for beiging
publisher MDPI AG
series Biomedicines
issn 2227-9059
publishDate 2020-11-01
description Recent preclinical data show that sodium glucose cotransporter 2 (SGLT2) inhibitors are able to reduce weight gain and induce beiging in white adipose tissue (WAT). We have previously shown that in neurogenic hypertensive Schlager (BPH/2J) mice, treatment with the SGLT2 inhibitor, Dapagliflozin, reduced blood pressure and prevented weight gain. Here we show that chemical sympathetic denervation achieved by systemic administration of 6-hydroxy-dopamine (6-OHDA) reduces body weight and the heightened sympathetic nervous system (SNS) innervation in WAT. Furthermore, we demonstrate that 2 weeks of Dapagliflozin treatment increases SNS innervation in WAT of hypertensive mice. This increase is accompanied by a non-significant elevation in mRNA levels of the <i>Ucp1</i> and <i>Pgc-1α</i> genes, which are markers of beiging. No significant difference in the mRNA levels of the inflammatory mediators <i>Il-6</i> and <i>Tnf-α</i> were detected in WAT of Dapagliflozin treated mice. These findings suggest that SGLT-2 inhibitor-associated prevention of weight gain may be mediated, at least in part, by inducing the beiging of WAT.
topic sympathetic nervous system
sodium glucose cotransporter 2 inhibition
Dapagliflozin
beiging
adipose tissue
hypertension
url https://www.mdpi.com/2227-9059/8/11/514
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