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. 2022 Aug 22;4(8):1071–1083. doi: 10.1038/s42255-022-00617-6

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© The Author(s) 2022

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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Extended Data Fig. 4 — Immunofluorescence (a) and quantification (b,c) of cFos positive neurons in the ventromedial hypothalamus (VMH) and dorsomedial hypothalamus (DMH) (n = 4 male 47-wk old C57BL/6 J mice each group, scale bar: 100 µm). Representative immunofluorescence image of Cyanine 5 (Cy5) labeled appearance of GLP-1RA and GLP-1RA/Tesaglitazar in the ARC of 49-wk old male C57BL/6 J DIO mice after 90 min of treatment with a single s.c. dose of 150 nmol/kg of either GLP-1RA-Cy5 or GLP-1RA/Tesaglitazar-Cy5 (n = 3/4 mice; scale bar: 50 µm) (d). Neuronal markers in the hypothalamic proteome (e). To illustrate the large dynamic range, quantified proteins across all hypothalamic samples were ranked and plotted according to their median Intensity. Marker proteins of different neuronal subtypes are highlighted in blue. Data in (b,c) were analyzed by 1-way ANOVA and Fisher’s LSD test. Data represent means ± SEM; asterisks indicate * p < 0.05, ** p < 0.01, *** p < 0.001. Exact p-values for treatment effects are (b) p = 0.0388 (Vhcl vs. GLP-1RA) and p = 0.0299 (Tesaglitazar vs. GLP-1RA); (c) p = 0.0269 (Vhcl vs. GLP-1RA/Tesaglitazar), p = 0.0446 (GLP-1RA vs. Tesaglitazar) and p = 0.0082 (GLP-1RA vs. GLP-1RA/Tesaglitazar).

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