Figure 3. Mutations in p38A and chico attenuate high sucrose-induced heart deterioration.

(A) Mutations in p38A enhanced developmental delay of larvae fed an HSD. Eggs were collected onto LSD or HSD food for 16 hours, then permitted to mature at 25°C. Time to pupariation was scored daily. HSD feeding resulted in two days' development delay for w¹¹¹⁸ flies. On low sucrose food, p38A mutations exhibited a slight delay compared to w¹¹¹⁸ controls; an HSD led to a four-day delay to pupariation. (B) Mutant p38A flies fed high dietary sucrose exhibited reduced life span. Experiments for both p38A mutants and w¹¹¹⁸ controls were performed at 22°C due to poor viability of developing p38A mutant flies grown at 25°C on an HSD. The average life span of p38A flies was ten days shorter than w¹¹¹⁸ controls fed an HSD. (C) Loss of p38A activity did not alter high dietary sucrose-induced cardiac arrhythmia. Arrhythmia index obtained from w¹¹¹⁸ controls and p38A mutants. The differences between LSD and HSD both in wild type controls and p38A mutants were significant (*P = 1.54E-17, and 1.20E-08, respectively, by F-test). However, there was no difference between w¹¹¹⁸ controls and p38A mutants. Data are means ± SE. (D) No difference in fractional shortening was observed between w¹¹¹⁸ controls and p38A mutants grown in either an LSD or an HSD. Data indicate mean ± SE. (E) Heart period was increased in p38A mutants fed an HSD. The heart period of p38A mutants fed on HSD was 0.86 second, compared to 0.60 second in w¹¹¹⁸ controls (*P = 0.008 by t-test). Data indicate mean ± SE. (F) Diastolic interval was increased in p38A mutants fed an HSD. Diastolic interval of p38A mutants fed an HSD was 0.64 second, compared to 0.39 second in w¹¹¹⁸ controls (*P = 0.01 by t-test). Data indicate mean ± SE. (G) Systolic interval was increased in in p38A mutants fed an HSD. Systolic interval of p38A mutants fed an HSD was 0.25 second, compared to 0.21 second in w¹¹¹⁸ controls (*P = 0.02 by t-test). Data indicate mean ± SE. (H) No difference was observed in developmental rates between w¹¹¹⁸ controls and chico¹/+ adults fed either an LSD or HSD. Data indicate mean ± SE. (I) Increased life span was observed in chico¹/+ adults compared to w¹¹¹⁸ controls when both were fed an LSD. However, the observed average life span in HSD is 35 days in chico¹/+ mutants, the same as w¹¹¹⁸ controls. Data indicate mean ± SE. (J) chico¹ mutation did not alter high dietary sucrose-induced cardiac arrhythmia. Arrhythmia index obtained from w¹¹¹⁸ controls and chico¹/+ mutants. The differences between LSD and HSD both in wild type controls and chico¹/+ mutants were significant (*P = 1.54E-17, and 2.10E-10, respectively, by F-test). However, there was no difference between w¹¹¹⁸ controls and chico¹/+ mutants (P = 0.20 by F-test). Data indicate mean ± SE. (K) Heart period was increased in chico¹/+ mutants fed with an LSD or HSD. Heart period of chico¹/+ mutants raised on low sucrose was 0.94 second, compared to 0.68 second of w¹¹¹⁸ controls (*P = 0.004 by t-test). Heart period of chico¹/+ mutants raised on an HSD was 0.91 second, compared to 0.60 second of w¹¹¹⁸ controls (*P = 0.0008 by t-test). Data indicate mean ± SE. (L) chico¹/+ flies exhibited significantly reduced fractional shortening in both LSD and HSD. Fractional shortening of chico¹/+ mutants raised on low sucrose was 37%, compared to 42% of w¹¹¹⁸ controls (*P = 0.006 by t-test). Fractional shortening of chico¹/+ mutants raised on an HSD was 34%, compared to 40% of w¹¹¹⁸ controls (*P = 0.001 by t-test). Data are means ± SE. (M) chico¹/+ flies exhibited significantly reduced diastole on both LSD and HSD. Diastole of chico¹/+ mutants raised on low sucrose was 49.9 microns, compared to 62.9 microns of w¹¹¹⁸ controls (*P = 0.0009 by t-test). Diastole of chico¹/+ mutants raised on an HSD was 45.8 microns, compared to 68.1 microns of w¹¹¹⁸ controls (*P = 2.14E-08 by t-test). Data are means ± SE. (N) Significantly reduced systole of chico¹/+ flies was observed in both LSD and HSD. Systole of chico¹/+ mutants raised on low sucrose was 31.6 microns, compared to 36.6 microns of w¹¹¹⁸ controls (*P = 0.03 by t-test). Systole of chico¹/+ mutants raised on an HSD was 30.2 microns, compared to 40.0 microns of w¹¹¹⁸ controls (*P = 0.0002 by t-test). Data are means ± SE. See also Videos S4, S5.