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

• Published in: Biomedicines Vol. 8; no. 11; p. 514
• Main Authors: Matthews, Jennifer R., Herat, Lakshini Y., Magno, Aaron L., Gorman, Shelley, Schlaich, Markus P., Matthews, Vance B.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 18.11.2020; MDPI
• Subjects: Adipose tissue; beiging; Blood pressure; Body fat; Body weight; Body weight gain; Dapagliflozin; Denervation; Diet; Dopamine; Energy; Glucose; Hypertension; Inflammation; Innervation; Interleukin 6; mRNA; Nervous system; Obesity; sodium glucose cotransporter 2 inhibition; Sympathetic nervous system; Thermogenesis; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Australia; United States > US
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines8110514

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.