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

Figures

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  Figure 1. Chemical denervation with 6-hydroxydopamine (6-OHDA) significantly reduced body weight in Blood Pressure High/2J (BPH/2J) mice, n = 4 mice/group. * p < 0.002; all data presented as mean ± standard error of the mean (SEM).

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  Figure 2. Chemical denervation with 6-OHDA significantly reduces sympathetic nervous system (SNS) innervation in white adipose tissue (WAT). (a,b) Representative immunohistochemistry images of tyrosine hydroxylase expression in WAT. Tyrosine hydroxylase (TH) staining is brown in color and is indicated with arrows. Insets indicate close-ups of TH staining. Size bar = 100 µm. Magnification 200×. (c) Quantitation of tyrosine hydroxylase expression in WAT from BPH/2J mice, n = 3–5 mice/group. * p < 0.05; all data are presented as mean ± SEM.

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  Figure 3. Representative image of glucose levels in urine after 11 days of Sodium glucose cotransporter 2 (SGLT2) inhibition. Dapagliflozin was administered at a dose of 40 mg/kg. Yellow = 0 mmol/L glucose and blue = 278 mmol/L glucose.

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  Figure 4. SGLT2 inhibition promotes increased SNS innervation in WAT. (a–c) Representative immunohistochemistry images of tyrosine hydroxylase expression in WAT. Tyrosine hydroxylase staining is brown in color and is indicated with arrows. Insets indicate close-ups of TH staining. Size bar = 100 μm. Magnification 200×. Brown adipose tissue like morphology is indicated with a white asterisk. (d) Quantitation of tyrosine hydroxylase expression in WAT from BPH/2J mice; n = 9–11 mice/group. * p = 0.011. (e) Norepinephrine in WAT from BPH/2J mice; n = 7–8 mice/group. All data are presented as mean ± SEM.

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  Figure 5. Inhibition of SGLT2 promotes elevation of markers of BAT in WAT. (a) Pgc-1a mRNA expression and (b) Ucp1 mRNA expression; n = 7–8 mice/group. All data are presented as mean ± SEM.

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  Figure 6. The effect of SGLT2 inhibition on pro-inflammatory cytokine expression in WAT. (a) Interleukin (Il-6) mRNA expression and (b) Tnf-α mRNA expression; n = 7–8 mice/group. All data are presented as mean ± SEM.