a, Schematic depiction of the experimental design for inducing DARS2 deletion in mice fed with a FFD created with BioRender.com. 8-12-week-old mice were fed with an equal mixture of normal chow diet (NCD) and FFD for 4 days, which was followed by 14 days FFD feeding and sacrifice 7 days after the last tamoxifen injection. b, Graph depicting relative body weight change in FFD-fed Dars2fl/fl (n = 18) and DARS2tamIEC-KO (n = 20) mice after tamoxifen injection. c, Immunoblot analysis with the indicated antibodies of small intestinal IEC protein extracts from FFD-fed Dars2fl/fl (n = 6) and DARS2tamIEC-KO (n = 8) mice. α-tubulin was used as loading control. d, Representative images of sections from the distal SI of FFD-fed Dars2fl/fl and DARS2tamIEC-KO mice 7 days after the last tamoxifen injection stained with H&E, ORO and COX/SDH or immunostained for PLIN2 and Ki67. Scale bar, 50 μm. e, Graph depicting relative mRNA levels of stem cell genes analysed by RT-qPCR and normalized to Tbp in the SI of Dars2fl/fl (n = 8) and DARS2tamIEC-KO (n = 8) mice 7 days after tamoxifen injection. f, Graphs depicting the concentration of glucose, total cholesterol and TAGs in sera from Dars2fl/fl (n = 6) and DARS2tamIEC-KO (n = 6) mice fed with FFD 7 days upon the last tamoxifen injection. In e and f, dots represent individual mice. In b, e and f 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) and two-sided nonparametric Mann-Whitney U -test (e, f). In c, each individual lane represents one mouse. For gel source data, see Supplementary Fig. 1. In d, histological images shown are representative of the number of mice analysed as indicated in Supplementary Table 4.
Source Data