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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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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