Figure 3. Fat-derived exosomal miRNAs regulate hepatic FGF21 and transcription.
(a) Enzyme-linked immunoassay (ELISA) of FGF21 in serum of ADicerKO and control littermates (n=4/group, p=0.028, two-tailed Mann-Whitney U-test). (b) qPCR of hepatic FGF21 mRNA in Lox and ADicerKO mice (n=4/group, p=0.028, two-tailed Mann-Whitney U-test). (c) Serum FGF21 of ADicerKO (+sham surgery), WT mice (+sham surgery) and ADicerKO transplanted groups (n=3/group, p=0.019, WT vs KO+BAT, two-tailed t-test). (d) qPCR of hepatic FGF21 mRNA of mice in Panel c (n=3/group, p=0.046, Cont vs KO+BAT, two-tailed t-test). (e) FGF21-3’UTR luciferase activity after incubation of AML-12 cells with exosomes from Lox (exoWT), ADicerKO (exoKO), 10 nM free miR-99b or exosomes derived from ADicerKO mice electroporated with miR-99b (exoKO+miR-99b) (n=3/group, p=0.008, WT vs KO, p=0.008, KO vs. KO+99b, two-tailed t-test) (f) FGF21-3’UTR activity after incubation of AML-12 cells with exosomes from ADicerKO, Lox littermates, or ADicerKO mice and electroporated to introduce miR-99a, miR-99b, miR-100 or miR-466i. (n=3/group, p=0.0007, exoWT vs. exoKO, p=0.002, exoKO vs. exoKO+99b, two-tailed t-test).