Fig. 4: General EAA deficiency coupled with a deficiency in GSH partially phenocopies cysteine deficiency.
From: Unravelling cysteine-deficiency-associated rapid weight loss
a, GSH levels in liver and muscle of CR male Cse+/− and Cse−/− mice at day 2 on the no-Cys diet. n = 7 per group. b, Representative IHC staining (n = 4 per group) of NRF2 and NQO1 in the liver of Cse+/− and Cse−/− mice on a CR no-Cys diet at day 3. c, The p-eIF2α/eIF2α ratio in Cse+/− and Cse−/− mice on a CR no-Cys diet at day 2. n = 5 (Cse+/−) and n = 6 (Cse−/−). d,e, The GDF15 (d) and FGF21 (e) serum levels at day 2 of CR no-Cys diet. n = 8 (Cse+/−, GDF15), n = 7 (Cse−/−, GDF15), n = 5 (Cse+/−, FGF21) and n = 4 (Cse−/−, FGF21). f, ACC1 protein levels normalized to β-tubulin in Cse+/− and Cse−/− mice at day 2 on a CR no-Cys diet. n = 4 per group. g,h, The FFA (g) and TG (h) serum levels at day 2 of a CR no-Cys diet. n = 5 (Cse+/−), n = 6 (Cse−/−). i, Body-weight measurements of Cse+/− and Cse−/− mice on different diets. n ≥ 4 in each group. j,k, Representative bulk liver mRNA-seq data for multiple groups represented as a heat map for genes in ISR and OSR (j), and those related to cholesterol and lipid metabolism (k). A complete list of differentially expressed genes for all sequenced samples is presented in Supplementary Table 2. l–o, The p-eIF2α/eIF2α ratio in the liver (l), liver GSH (m), ACC1 protein levels normalized to β-actin (n) and serum GDF15 (o) in CR Cse−/− mice on a no-Cys diet compared with CR Cse−/− mice on a no-Trp + BSO diet at day 2. n = 5 (l) and n = 4 (m–o) per group. p, Summary of the effects of no-Trp, no-Cys and no-Trp + BSO diets in Cse−/− mice. WL, weight loss. The diagram in p was created using BioRender. Statistical analysis was performed using unpaired t-tests (a and d–h). Data are mean ± s.e.m. **P < 0.01, ****P < 0.0001. Scale bars, 20 μm (left) and 100 μm (right).
