Transaldolase deficiency causes a starvation-like response that decreases animal fat content and rewires lipid metabolism gene expression.

<p><b>(A)</b> Intestinal fat staining decreases from RNAi knockdown of <i>tald-1</i> or <i>cco-1</i>. Oil Red O (ORO) staining was performed on day 3 from hatching animals propagated at 20°C. Scale bar, 50 μm. <b>(B)</b> Quantification of ORO staining within anterior intestine (N = 2 independent experiments, pooled individual worm values, error bars indicate s.e.m., student’s t-test with Bonferroni’s correction). <b>(C)</b> RNAi knockdown of <i>tald-1</i> causes an increase in adipose triglyceride lipase ATGL-1 protein levels. Scale bar, 200 μm. <b>(D)</b> Mean relative fluorescence of ATGL-1::GFP signal in animals grown on <i>tald-1(RNAi)</i> or <i>cco-1(RNAi)</i>. Fluorescence is calculated relative to <i>EV(RNAi)</i> controls (N = 4 independent experiments, pooled individual worm values, error bars indicate s.e.m., student’s t-test with Bonferroni’s correction). <b>(E)</b> RNAi knockdown of <i>tald-1</i> or <i>cco-1</i> causes a decrease in stearoyl-CoA desaturase <i>fat-7p</i>::<i>gfp</i> reporter expression. Scale bar, 200 μm. <b>(F)</b> Mean relative fluorescence of <i>fat-7p</i>::<i>gfp</i> reporter animals grown on <i>tald-1(RNAi)</i> or <i>cco-1(RNAi)</i>. Fluorescence is calculated relative to <i>EV(RNAi)</i> controls (N = 3 independent experiments, pooled individual worm values, error bars indicate s.e.m., student’s t-test with Bonferroni’s correction). <b>(G)</b> Gene expression of starvation-responsive lipid metabolism genes is altered in <i>tald-1(RNAi)</i> animals. Log2 fold change calculated to emphasize the increases and decreases in gene expression levels from RNAi treatments (N = 6–8 independent experiments, error bars indicate s.e.m., paired student’s t-tests with Bonferroni’s correction). <b>(H)</b> RNAi knockdown of <i>tald-1</i> does not robustly extend lifespan of BD animals. N2 fed <i>EV(RNAi)</i> (mean 18.2±0.2 days, n = 161), N2 fed <i>tald-1(RNAi)</i> (mean 20.4±0.2 days, n = 151), BD animals developed on <i>EV(RNAi)</i> (mean 20.2±0.2 days, n = 123), BD animals developed on <i>tald-1(RNAi)</i> (mean 21.5±0.3 days, n = 150). Lifespans were performed at 25°C, with one experiment shown. <b>(I)</b> RNAi knockdown of <i>cco-1</i> extends lifespan dissimilar from BD. N2 fed <i>EV(RNAi)</i> (mean 18.2±0.2 days, n = 161), N2 fed <i>cco-1(RNAi)</i> (mean 24±0.3 days, n = 156), BD animals developed on <i>EV(RNAi)</i> (mean 20.2±0.2 days, n = 123), BD animals developed on <i>cco-1(RNAi)</i> (mean 27.1±0.3 days, n = 148). Lifespans were performed at 25°C, with one experiment shown. <b>(J)</b> RNAi knockdown of <i>tald-1</i> does not require NHR-49 for lifespan extension. N2 fed <i>EV(RNAi)</i> (mean 17.5±0.1 days, n = 366), N2 fed <i>tald-1(RNAi)</i> (mean 20.1±0.1 days, n = 397), <i>nhr-49(nr2041)</i> fed <i>EV(RNAi)</i> (mean 11.5±0.1 days, n = 310), <i>nhr-49(nr2041)</i> fed <i>tald-1(RNAi)</i> (mean 12.9±0.1 days, n = 333). Lifespans were performed at 25°C, with pooled data from three independent experiments shown. <b>(K)</b> RNAi knockdown of <i>cco-1</i> does not require NHR-49 for lifespan extension. N2 fed <i>EV(RNAi)</i> (mean 17±0.1 days, n = 532), N2 fed <i>cco-1(RNAi)</i> (mean 22.6±0.2 days, n = 344), <i>nhr-49(nr2041)</i> fed <i>EV(RNAi)</i> (mean 11.1±0.1 days, n = 495), <i>nhr-49(nr2041)</i> fed <i>cco-1(RNAi)</i> (mean 15±0.1 days, n = 489). Lifespans were performed at 25°C, with pooled data from four independent experiments shown. Lifespans in this figure are indicated as mean±s.e.m. and statistical analysis is provided in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006695#pgen.1006695.s011" target="_blank">S1 Table</a>. In this figure, statistics are displayed as: * <i>p</i><0.05, ** <i>p</i><0.01, *** <i>p</i><0.001.