Fig. 4: The JAK–STAT signalling pathway regulates Pepck1 and Pdk expression in the fat body. | Nature Metabolism

Fig. 4: The JAK–STAT signalling pathway regulates Pepck1 and Pdk expression in the fat body.

From: Hepatic gluconeogenesis and PDK3 upregulation drive cancer cachexia in flies and mice

Fig. 4

a,b, Quantitative reverse transcription PCR (qRT–PCR) of Pepck1 (a) and Pdk (b) mRNA in the fat body of fed, starved, and refed flies at day 6 (n = 3). c,d, Pepck1 (c) and Pdk (d) mRNA in the fat body of control, Yki flies, and Yki flies with fat-body InR-ca (constitutive-activated form of InR) expression at day 8 (n = 3). e,f, Pepck1 (e) and Pdk (f) mRNA in the fat body of flies with or without ISC Upd3 expression at day 8 (n = 3). g, Data from the ChIP–seq database indicating enrichment of Stat92e binding at the Pepck1 and Pdk gene regions. The transcript isoforms Pepck1-RA and Pdk-RD were used to indicate the gene regions. Inverted triangle, STAT-binding motif (2N, TTCNNGAA; 3N, TTCNNNGAA; 4N, TTCNNNNGAA). h, ChIP revealed the enrichment of haemagglutinin (HA)-tagged Stat92E binding at the Pepck1 and Pdk gene regions, shown by fold changes relative to control IgG at day 8 (n = 3 biological replicates). Neg, negative control. i, Images of gut tumours and phenotypes of Yki flies with or without fat-body hop or Stat92e depletion at day 6. j, Quantification of gut tumours (GFP signal, arbitrary units) of Yki flies with or without fat-body hop or Stat92e depletion at day 6 (n = 12). k, Total pH3 counts per gut of control flies and Yki flies with or without fat-body hop or Stat92e depletion at day 6 (n = 10). l, Quantification of bloating phenotypes (A/H ratio) of Yki flies with or without fat-body hop or Stat92e depletion at day 6 (n = 9). m, Body-fluid levels of Yki flies with or without fat-body hop or Stat92e depletion at day 6 (n = 4). n,o, Pepck1 (n) and Pdk (o) expression in the fat body of control, Yki flies, and Yki flies with fat-body hop depletion at day 6 (n = 3). p,q, Pepck1 (p) and Pdk (q) expression in the fat body of Yki flies and Yki flies with fat-body Stat92e depletion at day 6 (n = 3). r,s, Whole-body trehalose (r) and glucose (s) levels of control (n = 8), Yki flies (n = 8), and Yki flies with fat-body hop (n = 5) or Stat92e (n = 6) depletion at day 6. Statistical significance was assessed using the unpaired two-sided Student’s t-test (e,f,p,q) and ordinary one-way ANOVA (ad,h,jo,r,s). Error bars indicate the s.d., with the mean as the centre. See also Extended Data Fig. 4.

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