Fig. 5: TRPA1 vagal neurons mediate fat-specific preference.
a, Single-cell RNA-seq atlas of nodose ganglia37, showing vagal clusters for VIP (blue), Trpa1 (red), Gpr65 (orange), Calca (green), Oxtr (brown) and Piezo2 (purple). b, The vagal cluster expressing TRPA1 (Trpa1-GCaMP6s) responded selectively to intestinal delivery of fat (10% LA), but not sugar (500 mM Glu) or amino acid (250 mM amino acids mixture) stimuli. The heat maps show z-score-normalized fluorescence traces. Of 163 imaged neurons from 5 ganglia, approximately 24% responded to fat. See Extended Data Fig. 9 for imaging results for the other vagal clusters. c, Left, strategy for silencing of TRPA1 neurons in the vagal ganglia by bilateral injection of AAV-DIO-TetTox into the nodose of Trpa1-cre mice. Fat and sugar preference tests on control mice (middle) and mice with silenced TRPA1-expressing vagal neurons (Trpa1-Tx) (right). Control mice develop strong preference for fat and sugar after 48 h (n = 7). By contrast, silencing of TRPA1 vagal neurons abolishes the development of fat but not sugar preference (n = 6, right). Two-sided Mann–Whitney U-test, control versus Trpa1-Tx for sugar, P = 0.23; control versus Trpa1-Tx for fat, P = 1.1 × 10−3. Data are mean ± s.e.m.
