Figure 7.

dilp5 is required for dietary sugar-enrichment-induced decline in sweet taste and preference. A, Preference of mated females prefed on indicated diet for 4 d and tested in binary choice assays with 5 mm sucrose (blue dye) against 1% yeast extract (pink dye). Genotypes were w¹¹¹⁸ (control, n = 8 balanced, 8 sugar-enriched), dilp2 (n = 7 balanced, 8 sugar-enriched), dilp3 (n = 7 balanced, 6 sugar-enriched), and dilp5 (n = 7 balanced, 9 sugar-enriched). dilp3 and dilp5 mutants were verified by genomic PCR (see Extended Data Fig. 7-1). Feeding participation of females prefed on balanced or sugar-enriched diet is shown in Extended Data Figure 7-2. B, Preference of mated females prefed on indicated diet for 1 d and tested in binary choice assays with 5 mm sucrose (blue dye) against 1% yeast extract (pink dye). Genotypes were w¹¹¹⁸ (control, n = 19 balanced, 17 sugar-reduced), dilp5 (n = 12 balanced, 12 sugar-reduced). C, Representative traces obtained from dilp5 mutant females fed on indicated diet for 4 d. D, Ratio of mean sweet neuron response of flies fed on sugar-enriched diet (test) to that from flies fed on balanced diet (control) for 4 d. Mean neuronal responses are shown in Extended Data Figure 7-3. Recordings were taken from labellar L-type sensilla in mated females. Genotypes were as follows: w¹¹¹⁸ (control) and dilp5, n = 19–30 sensilla from four to six flies. The dotted line indicates a ratio of 1, i.e., equal taste sensitivity to sucrose in test and control flies. E, Preference of mated females prefed on indicated diet for 4 d and tested in binary choice assays with 5 mm sucrose (blue dye) against 1% yeast extract (pink dye). Genotypes were as follows: dilp2-Gal4 (n = 9 balanced, 10 sugar-enriched), UAS-dilp5 RNAi (n = 6 balanced, 6 sugar-enriched), dilp2>dilp5 RNAi (n = 10 balanced, 12 sugar-enriched), UAS-TNTG (n = 9 balanced, 9 sugar-enriched), and dilp2>TNTG (n = 17 balanced, 17 sugar-enriched). Expression of dilp5 in dilp2>dilp5 RNAi flies was tested by qRT-PCR (see Extended Data Fig. 7-4). F, Preference of mated female flies prefed on indicated diet for 4 d and tested in binary choice assays with 2 mm sucrose mixed with 25 mm each of serine, phenylalanine, and threonine (sucrose + 3AA, pink dye) against 2 mm sucrose alone (blue dye). Genotypes were as follows: w¹¹¹⁸ (control, n = 6 balanced, 6 sugar-enriched), dilp5 (8 balanced, 10 sugar-enriched). G, Preference of mated females prefed on indicated diet for 4 d and tested in binary choice assays with 5 mm sucrose (blue dye) against 1% yeast extract (pink dye). Genotypes were as follows: w¹¹¹⁸ (control, n = 9 balanced, 9 sugar-enriched), InR¹ (BL11661)/InR² (BL9646; n = 6 balanced, 6 sugar-enriched). H, Preference of mated females prefed on indicated diet for 4 d and tested in binary choice assays with 5 mm sucrose (blue dye) against 1% yeast extract (pink dye). Genotypes were as follows: UAS-InR RNAi (n = 7 balanced, 6 sugar-enriched), elav-Gal4 (n = 9 balanced, 8 sugar-enriched), elav-Gal4 > UAS-InR RNAi (n = 6 balanced, 6 sugar-enriched). I, Preference of mated females prefed on indicated diet for 4 d and tested in binary choice assays with 5 mm sucrose (blue dye) against 1% yeast extract (pink dye). Genotypes were as follows: UAS-InR RNAi (control n = 6 balanced, 6 sugar-enriched), v-Glut>UAS-InR RNAi (n = 7 balanced, 7 sugar-enriched), Gad1>UAS-InR RNAi (n = 7 balanced, 7 sugar-enriched), Ple>UAS-InR RNAi (n = 6 balanced, 7 sugar-enriched), Trh>UAS-InR RNAi (n = 8 balanced, 8 sugar-enriched), Tdc2>UAS-InR RNAi (n = 7 balanced, 7 sugar-enriched), npF>UAS-InR RNAi (n = 7 balanced, 7 sugar-enriched). Expression of InR in Trh-GAL4>UAS-InR RNAi flies was measured by qRT-PCR (see Extended Data Fig. 7-5). For all except C, D, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ns - not significant, two-way ANOVA with Sidak's post hoc multiple comparisons test.