Positive regulation of <i>sNPF/NPY</i> by the Mnb/Dyrk1a-Sir2-FOXO pathway.

<p>(A) Sirt1 phosphorylation was increased in mouse GT1-7 cells transfected with <i>Dyrk1a</i> or treated with NPY but reduced in cells transfected with <i>Dyrk1a</i> siRNA or <i>Dyrk1a</i> siRNA co-treated with NPY. (B) <i>NPY</i> mRNA was increased in GT1-7 cells transfected with <i>Dyrk1a</i> or treated with NPY peptide, but reduced in cells transfected with <i>Dyrk1a</i> siRNA, <i>Dyrk1a</i> siRNA co-treated with NPY, or <i>Dyrk1a</i> co-treated with Sirt1 inhibitor EX527. (C) FoxO1 acetylation was reduced in GT1-7 cells transfected with <i>Dyrk1a</i> or treated with NPY peptide, but FoxO1 acetylation was increased in cells transfected with <i>Dyrk1a</i> siRNA, <i>Dyrk1a</i> siRNA co-treated with NPY, or <i>Dyrk1a</i> co-treated with Sirt1 inhibitor EX527. (D, E) <i>sNPF</i> mRNA (D) and food intake (E) were reduced when <i>Sir2</i> or <i>dFOXO</i> were inhibited while <i>mnb</i> was overexpressed in <i>sNPFR1</i> expressing neurons relative to levels observed for <i>mnb</i> overexpression alone (<i>sNPFR1>mnb</i>). (F) <i>sNPF</i> and <i>mnb</i> mRNA increased in adults starved 12 h. (G) dFOXO binding to the promoter region of the <i>sNPF</i> gene in adult flies starved 12 h was elevated relative to the <i>Act5c</i> and fed controls (ChIP-chip). Data are presented as means ± s.e.m. from three independent experiments. <i>*P</i><0.05, <i>**P</i><0.001 (One-way ANOVA analysis).