Fig. 7
SIRT1 enhances KLB-AKT signalling and promotes FGF21-induced Oxt expression. a–d Effects of Sirt1 manipulation on gene expression in hypothalamic N41 cells. Sirt1 expression was manipulated by viral vectors to different degrees. Sirt1 expression in untreated (CO), control (GFP) and viral infected cells (red, Sirt1 overexpressing; blue, Sirt1 silencing). Shading indicates low (light) to high (dark) MOIs or knockdown efficiencies. Manipulating Sirt1 expression (a) affected expression of Oxt (b) and Klb (c), but not Fgfr1 (d) (n = 4 per group). e, f Hypothalamic Klb and Fgfr1 mRNA expression in WT, NS-OE (red) and NS-KO (blue) mice (n = 6 per group). g, h Effects of Sirt1 overexpression (top) and Sirt1 silencing (bottom) on FGF21-induced Oxt expression. N41 cells were treated with or without 100 nM mFGF21 for 8 h; expression levels of Sirt1 (g) and Oxt (h) (n = 3 per group). i Hypothalamic Oxt mRNA expression levels in to OS-OE and OS-KO mice after IP injection of mFGF21 (1 mg/kg) or water (vehicle) (n = 4 per group). j, k Effects of overexpressing (j) (n = 2 per group) or silencing (k) (n = 3 per group) Sirt1 expression on FGF21-induced intracellular signalling analysed by western blotting. After viral infection, N41 cells were incubated for 5 min in the absence or presence of 100 nM mFGF21. Data are shown as box and whisker plots (centre line, median; box limits, upper and lower quartiles; whiskers, the minimum and maximum value of a data set). *p < 0.05. Data in a–h were replicated more than three times, and data in j, k were replicated twice in the laboratory. See also Supplementary Fig. 6
