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. 2021 Mar 11;11:5637. doi: 10.1038/s41598-021-85051-6

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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NNMTi treatment combined with a lean diet switch accelerated weight and fat loss, promoting persistent weight and fat reductions without impacting food intake. Study timeline (a), body weight (b), fat mass (c), and average daily food intake (d) across the study period (n = 6–8/group); weights are in grams and age is in weeks (wk). Data are represented as mean ± SEM; treatment start is labeled by the black arrow and diet change by the grey arrow; the grey box represents the 3-day transition to diet followed by 2 days of sham injections. Body weight analyses demonstrated a significant main effect of treatment group (p < 0.0001), study day (p < 0.0001), and an interaction of treatment group by study day (p < 0.0001), rendering the NNMTi-treated group indistinguishable from the LD control group upon study completion. Fat mass demonstrated main effects of treatment group (p < 0.0001), study week (p < 0.0001), and a study week by treatment group interaction (p < 0.0001). Average daily food intake only demonstrated a significant effects of study week (p < 0.0001) and a study week by treatment group interaction (p < 0.0001). Mixed effects models (b,d); two-way repeated measures ANOVA (c). For a full list of statistical results, see Supplementary Table S1. LD lean diet, HFD high-fat diet, -T NNMTi-treated, -V vehicle-treated, WD Western diet; a, LD/LD-V vs. WD/WD-V; b, both WD/LD groups vs. LD/LD-V; c, both WD/LD groups vs. WD/WD-V; d, WD/LD-T vs. WD/LD-V. Labeled pairwise comparisons are significant (< 0.05) corrected (q) and uncorrected (p) for multiple comparisons; ‘ + ’, significant result with FDR correction only.