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. 2021 Jun 9;12:3486. doi: 10.1038/s41467-021-23856-9

Fig. 5. Reduced insulin/IGF signaling alters folic acid and methionine cycle intermediates.

Fig. 5

a Relative abundance of methionine cycle intermediates in daf-2 mutants and WT animals using targeted metabolomics. b Relative mRNA expression level of methionine restriction gene signature in daf-2 and daf-2;daf-16 backgrounds. dgn-1, ing-3, dapk-1, and daf-18 are upregulated and let-23 and ing-3 downregulated in the daf-2 background, independent of daf-16. c, e Targeted metabolomics of folic acid intermediates in brain and liver in wild-type and Irs1−/− full body knockout mice. Folic acid and THF increase in Irs1−/−, whereas 5MTHF decreases in the mutant. d, f Quantitation of methionine cycle intermediates in brain and liver in wild-type and Irs1−/− knockout mice. Methionine and SAM decrease and homocysteine increases in the mutant. a N = 4 independent biological replicates. b N = 3 independent biological replicates, c–f N = 5 mice, each dot represents a single animal. a–f Significance was assessed using one-way ANOVA Dunnett’s multiple comparisons test. *p < 0.5, **p < 0.01, ***p < 0.001. Data are presented as mean ± S.D. (Supplementary Table 6 for statistics).