Fig. 3: Upregulation of Pepck1 and Pdk in the fat body of Yki flies stimulates gluconeogenesis.
From: Hepatic gluconeogenesis and PDK3 upregulation drive cancer cachexia in flies and mice
a, A schematic of the gluconeogenesis pathway in Drosophila. b,c, Violin plots of expression levels of Pepck1 (b) and Pdk (c) at day 5 in the fat-body cell cluster; data were retrieved from snRNA-seq (Ctrl n = 1,263, Yki n = 1,788). Box plots show the medians (top centre line), means (bottom centre line), and the interquartile ranges. The whiskers of each box plot extend to the lowest and highest expression levels. d,e, Violin plots of expression levels of Pepck1 (d) and Pdk (e) at day 8 in the fat-body cell cluster retrieved from snRNA-seq (Ctrl n = 1,022, Yki n = 2,127). In the Ctrl group, box plots show the mean (top centre line) and median (bottom centre line); in the Yki group, the medians are represented by the top centre line and the means by the bottom centre line. Box plots also display interquartile ranges. The whiskers of each box plot extend to the lowest and highest expression levels. f, GSEA of the gluconeogenesis pathway, performed on fat-body genes retrieved from snRNA-seq. g,h, Whole-body trehalose (g) and glucose (h) levels at various tumour-induction time points (2, 4, and 8 days) (n = 4). i,j, Representative images of gut tumours and the phenotype of Yki flies with or without fat-body Pepck1 (i) and Pdk (j) depletion at day 6. k, Quantification of gut tumours (GFP signal) of Yki flies with or without fat-body Pepck1 and Pdk depletion at day 6 (n = 12). l, Total pH3 counts per gut of Yki flies with and without fat-body Pepck1 and Pdk depletion at day 6 (n = 9). m,n, The bloating rate quantification method (m) and results (n), represented by the abdomen to head size (A/H) ratio of Yki flies with or without fat-body Pepck1 and Pdk depletion at day 6 (n = 9). o, Body fluid levels of Yki flies with or without fat body Pepck1 and Pdk depletion at day 6 (n = 4). p,q, Whole-body trehalose (p) and glucose (q) levels of control flies, Yki flies, and Yki flies with fat-body Pepck1 depletion at day 6 (Ctrl n = 5, Yki n = 4, Yki with fat-body Pepck1 depletion n = 4). r,s, Whole-body trehalose (r) and glucose (s) levels of control flies, Yki flies, and Yki flies with fat-body Pdk depletion at day 6 (n = 4). t,u, Relative quantities of [13C3]oxaloacetate (t) and [13C3]phosphoenolpyruvate (u) in control flies, Yki flies, and Yki flies with fat-body Pdk depletion at day 6 (Ctrl n = 4, Yki n = 4, Yki with fat-body Pdk depletion n = 6). Statistical significance was assessed using unpaired two-sided Student’s t-test (k,n) and ordinary one-way ANOVA (g,h,l,o–u). The error bars indicate the s.d., with the mean at the centre. m was created in BioRender (https://BioRender.com/w65y109). See also Extended Data Fig. 3.
