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. 2018 Jan 8;8:55. doi: 10.1038/s41598-017-18388-6

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© The Author(s) 2017

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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Peripheral or central administration of Bace1 inhibitor reduces body weight and hyperleptinemia of DIO mice. (a) Hypothalamic Bace1 mRNA (n = 9–11), protein (n = 7–11) and activity (sAPPβ; n = 8) in sc vehicle or M-3 DIO mice. (b) Percentage body weight decrease and actual weight loss in DIO mice given sc vehicle or M-3 (n = 11). (c) qMR of DIO mice after sc vehicle or M-3 (n = 6–7/group). (d) Plasma leptin of DIO mice after sc vehicle or M-3 (n = 8–9/group). (e) Cumulative food intake of DIO mice given sc vehicle or M-3 (n = 11). (f) RER of DIO mice after sc vehicle or M-3 (n = 5–7/group). (g) Locomotor activity of naïve DIO mice and DIO mice after sc vehicle or M-3 (n = 6–7/group). (h) Agrp/Pomc and Npy/Pomc ratios for DIO mice after sc vehicle or M-3 (n = 12–14/group). (i) Hypothalamic sAPPβ of icv vehicle or M-3 DIO mice (n = 11–12/group). (j) Percentage body weight decrease and actual weight loss in DIO mice given icv vehicle or M-3 (n = 11). (k) Plasma leptin of DIO mice after icv vehicle or M-3 (n = 4–6/group). (l) Agrp/Pomc and Npy/Pomc ratios for DIO mice following icv vehicle or M-3 (n = 12–13/group). (m) Cumulative food intake of DIO mice given icv vehicle or M-3 (n = 7–9/group). Data are means ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 by 2-tailed unpaired Student’s t-test (a,d,f,h,i,k,l) body weight loss in (b,j), one-way ANOVA with Bonferroni’s multiple comparisons test (c,g) or repeated measures ANOVA with Sidak’s multiple comparisons test (b,e,j,m).