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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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Autores principales: Matthews, Jennifer R., Herat, Lakshini Y., Magno, Aaron L., Gorman, Shelley, Schlaich, Markus P., Matthews, Vance B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698773/
https://www.ncbi.nlm.nih.gov/pubmed/33218034
http://dx.doi.org/10.3390/biomedicines8110514
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author Matthews, Jennifer R.
Herat, Lakshini Y.
Magno, Aaron L.
Gorman, Shelley
Schlaich, Markus P.
Matthews, Vance B.
author_facet Matthews, Jennifer R.
Herat, Lakshini Y.
Magno, Aaron L.
Gorman, Shelley
Schlaich, Markus P.
Matthews, Vance B.
author_sort Matthews, Jennifer R.
collection PubMed
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 Ucp1 and Pgc-1α genes, which are markers of beiging. No significant difference in the mRNA levels of the inflammatory mediators Il-6 and Tnf-α 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.
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spelling pubmed-76987732020-11-29 SGLT2 Inhibitor-Induced Sympathoexcitation in White Adipose Tissue: A Novel Mechanism for Beiging Matthews, Jennifer R. Herat, Lakshini Y. Magno, Aaron L. Gorman, Shelley Schlaich, Markus P. Matthews, Vance B. Biomedicines Article 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 Ucp1 and Pgc-1α genes, which are markers of beiging. No significant difference in the mRNA levels of the inflammatory mediators Il-6 and Tnf-α 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. MDPI 2020-11-18 /pmc/articles/PMC7698773/ /pubmed/33218034 http://dx.doi.org/10.3390/biomedicines8110514 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Matthews, Jennifer R.
Herat, Lakshini Y.
Magno, Aaron L.
Gorman, Shelley
Schlaich, Markus P.
Matthews, Vance B.
SGLT2 Inhibitor-Induced Sympathoexcitation in White Adipose Tissue: A Novel Mechanism for Beiging
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698773/
https://www.ncbi.nlm.nih.gov/pubmed/33218034
http://dx.doi.org/10.3390/biomedicines8110514
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