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. 2021 Nov 26;55:101407. doi: 10.1016/j.molmet.2021.101407

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© 2021 The Authors

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

PMC Copyright notice

CCK^AP/NTSneurons are required for the anorectic and body-weight lowering effects of GLP-1R agonists. (A) Schematic of the strategy to inhibit CCK^AP/NTS neurons using Cre-dependent AAV expressing an eGFP-fused tetanus-toxin-light-chain (TeLC) and (B) TeLC-eGFP expression in CCK^AP/NTS neurons.(C) Food intake in control (CCK^AP/NTS-eGFP; n = 7) and CCK^AP/NTS-TeLC-eGFP (n = 8) mice injected with saline (F_(1,13) = 1.55, p = 0.2350) and (D) EX-4 (10 μg kg⁻¹, IP; F_(1,13) = 19.02, p = 0.0008).(E) EX-4 (20 μg kg⁻¹, IP, twice daily) suppresses body weight in control CCK^AP/NTS-eGFP (n = 7), but not in CCK^AP/NTS-TeLC-eGFP (n = 8) mice (Treatment: F_(1,13) = 56.23, p < 0.0001; Time: F_(7,91) = 22.21, p < 0.0001; Interaction: F_(7,91) = 7.48, p < 0.0001; two-way ANOVA. Delta BW: t (13) = 2.745,p = 0.0167). Data are presented as mean ± SEM. See also, Supplemental Fig. 1.