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. 2024 Jul 12;15:5857. doi: 10.1038/s41467-024-50157-8

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© The Author(s) 2024

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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Fig. 5 — a, b GSEA of lipid (a) and fatty acids (b) biosynthetic process for G6pd^KO;KL (n = 7 mice) and G6pd^WT;KL (n = 8 mice) lung tumors at 12 weeks post-tumor induction based on bulk-tumor mRNA-seq data. c Representative IHC images and quantification of pAMPK and pACC in G6pd^WT;K (Kras^G12D/+), G6pd^WT;KL and G6pd^KO;KL lung tumors at 12 weeks post-tumor induction. n = 10 images for each quantification. Scale bar = 100 μm. d Scheme of in vivo D₂O infusion to examine tumor de novo fatty acid synthesis (Created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license). e, f C16:0 (e) and C18:2 (f) deuterium (²H) labeling fraction in G6pd^WT;KL (n = 9 mice) and G6pd^KO;KL (n = 8 mice) lung tumors at 12 weeks post-tumor induction. g C16:0 pool size of G6pd^WT;KL (n = 9 mice) and G6pd^KO;KL (n = 8 mice) lung tumors at 12 weeks post-tumor induction. h, i Principal Component Analysis (PCA) (h) and Heatmap (i) of saponified fatty acids pool size of G6pd^WT;KL and G6pd^KO;KL lung tumors (n = 5 mice for G6pd^WT;KL, n = 4 mice for G6pd^KO;KL) and serum (n = 5 mice for G6pd^WT;KL, n = 3 mice for G6pd^KO;KL) in fasted state at 12 weeks post-tumor induction. j Scheme to examine the impact of high-fat diet (HFD) on KL lung tumorigenesis (Created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license). k Representative gross lung pathology from mice bearing G6pd^WT;KL (n = 4 mice for 7 weeks in normal diet (ND), n = 5 mice for 7 weeks in HFD, n = 8 mice for 11 weeks in ND, n = 6 mice for 11 weeks in HFD) and G6pd^KO;KL (n = 4 mice for 7 weeks in ND, n = 4 mice for 7 weeks in HFD, n = 11 mice for 11 weeks in ND, n = 10 mice for 11 weeks in HFD) lung tumors fed with ND or HFD. Scale bar = 1 cm. l Graph of wet lung weight from (k). m Representative H&E staining of scanned lung sections from (k). n, o Quantification of tumor number (n) and tumor burden (o) from (m). n is same with (k). p Representative IHC images and quantification of Ki67 in G6pd^WT;KL (n = 17 images for ND, n = 29 images for HFD) and G6pd^KO;KL (n = 17 images for ND, n = 21 images for HFD) lung tumors at 11 weeks post-tumor induction. Scale bar = 100 μm. Data are presented as mean ± SEM, significance was calculated by two-tailed unpaired t-test (g, i), one-way ANOVA followed by Bonferroni’s multiple comparisons test (c, p), two-way ANOVA followed by t-test (l, n, o). Source data are provided as a Source Data file.