Fig. 4: Parenchyma-projecting neurons regulate iBAT physiology, while blood vessel-projecting neurons influence systemic glucose metabolism.
From: Distinct sympathetic projections to brown fat regulate thermogenesis and glucose tolerance
a–d, The effects of chemogenetic activation of parenchyma-projecting SG2 neurons in anaesthetized mice: the experimental strategy to record from Vmat1-Cre mice injected with Cre-dependent hM3D–mCherry-expressing MaCPNS1 virus in iBAT (a); average traces of thermogenesis (ΔiBAT − LB, top) and blood flow (bottom) in iBAT recorded from mice injected with SAL and CNO (n = 14 mice) (b); and changes in temperature (c) and in blood flow (d) in iBAT following SAL or CNO treatment in mice shown in b. P < 0.001 for both measurements. e–h, The effects of chemogenetic activation of blood vessel-projecting SG1 neurons in anaesthetized mice: the experimental strategy to record from Rxfp1-Cre mice injected with Cre-dependent hM3D–mCherry-expressing MaCPNS1 virus in iBAT (e); average traces of thermogenesis (ΔiBAT − LB, top) and blood flow (bottom) in iBAT recorded from mice injected with SAL and CNO (n = 10 mice) (f); and changes in temperature (g) and in blood flow (h) in iBAT following SAL or CNO in mice shown in f. i–l, The effects of chemogenetic activation of parenchyma-projecting SG2 neurons in awake mice: a schematic of the random crossover experimental design to assess the impact of DCZ versus SAL treatment in awake Vmat1-Cre mice that received Cre-dependent hM3D–mCherry-expressing MaCPNS1 virus in iBAT (i); average traces of EE (n = 6 mice) (j); and changes in EE (k) and RER (l) following SAL or DCZ injection (n = 9, P = 0.04591 for k and P = 0.0031 for l). m–p, The effects of chemogenetic activation of arteriole-projecting SG1 neurons in awake mice: a schematic of the random crossover experimental design to assess the impact of DCZ versus SAL treatment in awake Rxfp1-Cre mice that received Cre-dependent hM3D–mCherry-expressing MaCPNS1 virus in iBAT (m); the average traces of EE (n = 8 mice) (n); and changes in EE (o) and RER (p) following SAL or DCZ injection in mice shown in n (P = 0.0188 for p). q,r, The effects of chemogenetic activation of parenchyma-projecting SG2 neurons in awake mice. The effect of DCZ or SAL delivered immediately before a glucose gavage on circulating glucose levels (q) and within-subject effects (DCZ minus SAL) on blood glucose levels (r) from the same mice shown in q. Data presented as the mean ± s.e.m. (n = 6 mice, tested in both conditions). s,t, Effects of chemogenetic activation of arteriole-projecting SG1 neurons in awake mice. The effect of DCZ or SAL delivered immediately before a glucose gavage on circulating glucose levels (s) and within-subject effects (DCZ minus SAL) on blood glucose levels (t) from the same mice shown in s (n = 8, tested in both conditions, P = 0.01377 at 15 min). u–w, The effects of chemogenetic inhibition of arteriole-projecting SG1 neurons in awake mice: a schematic of the random crossover experimental design to assess the impact of DCZ versus SAL treatment in awake Rxfp1-Cre mice that received Cre-dependent hM4Di–mCherry-expressing MaCPNS1 virus in iBAT (u); the effect of DCZ or SAL delivered immediately before a glucose gavage on circulating glucose levels (v) (n = 6 mice, tested in both conditions, P = 0.02997 at 15 min and P = 0.04776 at 30 min); and within-subject effects (DCZ minus SAL) on blood glucose levels (w) from the same mice shown in v. In b, f, j and n, the lines represent the means and shaded areas represent ± s.e.m. In c, d, g, h, k, l, o and p, dots represent average values and lines represent individual mice. Paired t-test, two tailed *P < 0.05, **P < 0.01 and ***P < 0.001. NS, not significant.
