Fig. 1: Chemogenetic stimulation of iBAT-projecting SNS neurons modulates iBAT functions and systemic metabolism.
From: Distinct sympathetic projections to brown fat regulate thermogenesis and glucose tolerance
a, A schematic illustration of retrograde labelling to sympathetic (yellow) and/or sensory (blue) ganglia with AAV injections into iBAT. b, Injections of GFP-expressing MaCPNS1 virus into iBAT of WT mice labelled neurons in the SG and DRG at C4, C6 and T1. Scale bar, 200 µm. c, Injections of Cre-dependent mCherry-expressing MaCPNS1 into iBAT of Th-Cre mice labelled neurons in the SG but not DRGs. Scale bar, 200 µm. d,e, Representative traces of thermogenesis (ΔiBAT − lower back (LB), top) and blood flow (bottom) in iBAT in a Th-Cre mouse injected with a control Cre-dependent mCherry-expressing MaCPNS1 virus (d) or with a Cre-dependent hM3D–mCherry-expressing MaCPNS1 virus (e). f,g, Change in temperature (f) and blood flow (g) in iBAT following SAL or CNO injection (n = 16 mice, tested in both conditions, P < 0.001). h, A schematic illustration of the random crossover experimental design to assess the impact of DCZ versus SAL treatment in awake Th-Cre mice that received Cre-dependent hM3D–mCherry-expressing MaCPNS1 virus in iBAT (data shown in i–m). i, The average traces of energy expenditure (EE). The solid lines represent means, shaded areas represent ± s.e.m. (n = 8 mice). j,k, Changes in EE (j) and RER (k) following SAL or DCZ injection (n = 16 mice each tested in both conditions, P < 0.001). l, The effect of DCZ or SAL delivered immediately before an oral glucose tolerance test (OGTT) on circulating glucose levels. Data presented as the mean ± s.e.m. (n = 19 mice, tested in both conditions, P = 0.0016 at 15 min). m, Within-subject effects (DCZ minus SAL) on blood glucose levels from the same mice shown in l. n, A schematic illustration of the random crossover experimental design to assess the impact of DCZ versus SAL treatment in awake Th-Cre mice that received Cre-dependent hM4Di–mCherry-expressing MaCPNS1 virus in iBAT (data shown in o and p). o, The effect of DCZ or SAL delivered immediately before a glucose gavage on circulating glucose levels. Data presented as the mean ± s.e.m. (n = 5 mice, P = 0.04271 at 15 min). p, Within-subject effects (DCZ minus SAL) on blood glucose levels from the same mice shown in o. In f, g, j and k, the dots represent average values and lines represent individual mice. Paired t-test, two tailed, no adjustments. **P < 0.01 and ***P < 0.001. Panel a created with BioRender.com.
