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. 2018 May 1;8:6789. doi: 10.1038/s41598-018-25098-0

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© The Author(s) 2018

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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ER stress mediates MCD diet-induced GDF15 expression. (a) Immunoblot analysis of liver lysates from C57BL/6 mice fed MCD diet for 8 weeks. Asterisk indicates a non-specific band. (b) Serum GDF15 (left panel, n = 6) and relative hepatic Gdf15 mRNA levels (middle panel, n = 4) in C57BL/6 mice 24 h after tunicamycin (Tu, 1 mg/kg) or vehicle (Veh) injection. Time-course of the changes in mouse liver Gdf15 mRNA level after Tu injection (right panel, n = 3). (c) Relative GDF15 mRNA level in HepG2 cells after incubation with Tu (5 μg/ml) or thapsigargin (Th, 1 μM) for 24 h (n = 3). (d,e) A heatmap showing relative expression of Gdf15 and upstream or downstream genes of CHOP, and Gdf15/Chop mRNA levels in the livers of Eif2ak3^Δhep mice (d, GSE29929) and Ern1^Δhep mice (e, GSE40515). (f) Relative Gdf15 mRNA level in Chop^–/– MEFs treated with Th (1 μM) (n = 3). (g) Serum GDF15 (n = 8–9) and relative hepatic Gdf15 or Chop mRNA levels (n = 5) in MCD diet-fed C57BL/6 mice treated with 4-PBA (1 g/kg/day) or vehicle (Veh) for 9 days. Data are means ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001.