Fig. 1: AstC secretion from the gut is nutrient-responsive and regulates organismal resistance to nutrient stress. | Nature Communications

Fig. 1: AstC secretion from the gut is nutrient-responsive and regulates organismal resistance to nutrient stress.

From: The gut hormone Allatostatin C/Somatostatin regulates food intake and metabolic homeostasis under nutrient stress

Fig. 1

a A screen of adult-midgut peptides identified those that affect starvation survival. Color scale indicates the number of standard deviations from the mean of all lines. Adult-restricted EEC-specific RNAi (b) or CRISPR-mediated knockout (c) of AstC prolongs female starvation survival (p < 0.0001). d Starvation induces AstC release from EECs (marked with anti-Pros). AstC staining is prominent in the R3 region (middle midgut) in fed females and is strongly reduced under starvation. AstC expression remains constant, Supplementary Fig. S1d. Representative of nine guts. Scale bars 50 μm. e AstC staining in R3 drops with starvation (p < 0.0001; results represent 9 guts, n = 145 fed and 72 starved cells). f AstC-expressing cells are abundant in female R3 and R4 (AstC > GFP, green) and less common in R2. Bottom: an enlargement of R3, in which calcium-LexA was measured. Image is representative of six guts. Scale bar 100 μm. g Female starvation survival is prolonged (p < 0.0001) with AstC knockdown in the AstC-producing EECs of the gut. h Starvation activates AstC-expressing EECs of R3, as measured by calcium-induced GFP expression. Scale bars 50 μm. These data represent analysis of 6 guts, n = 120 fed and 100 starved cells; p < 0.0001, and are quantified in (i). j TOR activity inhibits EEC AstC release. Expression of TSC1/2 in EECs for 6 h leads to a strong reduction in R3 AstC staining (results represent analysis of guts from at least 8 animals, n = 85 voilà> and voilà>TSC1/2 cells; p < 0.0001), despite an increase in AstC transcript levels (Supplementary Fig. S1h). k Inhibition of TOR in the AstC-producing cells alone using AstC> to conditionally express TSC1/2 also strongly reduced R3 EEC AstC staining, quantified in (l) (at least 9 guts, n = 99 AstC > and 99 AstC>TSC1/2 cells; p < 0.0001). Scale bars 50 μm. Error bars indicate SEM. ***p < 0.001. Statistical significance was determined using Kaplan–Meier log-rank tests (b, c, g) or two-tailed Mann–Whitney U test (e, i, j, l). Source data are provided as a Source data file.

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