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. 2023 Dec 20;625(7994):385–392. doi: 10.1038/s41586-023-06857-0

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© The Author(s) 2023

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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Extended Data Fig. 9 — a-n, Metabolic tracing studies performed in DARS2^tamIEC-KO mice 7 (a-f) and 5 days (a, d, g-n) upon the last tamoxifen injection. a, Schematic depiction of the experimental design of the oral fat tolerance test (OFTT) created with Biorender.com. On day 5 or 7 after the last tamoxifen injection, mice received an intravenous injection of the lipoprotein lipase inhibitor tyloxapol and were fasted for 2 h, followed by oral gavage with a lipid solution containing ³H-triolein and ¹⁴C-cholesterol. Afterwards, blood was collected from the tail vein for the indicated time points and the plasma appearance of the tracers was measured. b, c, g, h, Relative body weight change over the indicated time period (b, g) and body weight recorded on the day of sacrifice (c, h) of Dars2^fl/fl (n = 8) and DARS2^tamIEC-KO (n = 8) mice subjected to OFTT 7 days (b, c) or 5 days (g, h) upon tamoxifen. e, f, j, k, Relative body weight change over the indicated time period (e, j) and body weight recorded on the day of sacrifice (f, k) of Dars2^fl/fl (n = 7) and DARS2^tamIEC-KO (n = 8) mice subjected to OGFTT 7 days (e, f) or Dars2^fl/fl (n = 9) and DARS2^tamIEC-KO (n = 10) mice subjected to OGFTT 5 days (j, k) upon tamoxifen. d, Schematic depiction of the experimental design of the oral glucose fat tolerance test (OGFTT) created with BioRender.com. On day 5 or 7 after the last tamoxifen injection, mice were fasted for 2 h followed by oral gavage with ³H-triolein and ¹⁴C-DOG. Tissues were harvested 2 h after the oral gavage. i, Graphs depicting ³H-triolein, ¹⁴C-cholesterol and TAG content in portal plasma of Dars2^fl/fl (n = 8) and DARS2^tamIEC-KO (n = 8) mice subjected to OFTT after intravenous tyloxapol injection. l, Graph depicting relative organ weight of Dars2^fl/fl (n = 9) and DARS2^tamIEC-KO (n = 10) mice subjected to OGFTT. m, n, Graphs depicting counts of ³H-triolein (m) or ¹⁴C-DOG (n) in different organs and plasma from Dars2^fl/fl (n = 9) and DARS2^tamIEC-KO (n = 10) mice determined 120 min after oral gavage 5 days upon the last tamoxifen injection. In c, f, h, k, l, m and n, dots represent individual mice. In bar graphs data are represented as mean ± s.e.m. and P values were calculated by two-way ANOVA with Bonferroni’s correction for multiple comparison (b, e, g, j), two-sided nonparametric Mann-Whitney U -test (c, f, h, k), and unpaired two-sided Student’s t-test with no assumption of equal variance (i, l, m, n).

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