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. 2018 Jul 12;3(13):e95948. doi: 10.1172/jci.insight.95948

Figure 5. Fgf21 is a target of TTP.

Figure 5

(A) mRNA expression of putative Ttp-targeted hepatic secretory proteins in liver from WT and lsTtp-KO mouse fed normal chow (n = 10–12). (B) mRNA levels of putative Ttp-targeted hepatic secretory proteins in liver from WT and lsTtp-KO mouse fed HFD (n = 6–9). (C) Fasted lsTtp-KO mice have increased circulating FGF21 levels after 12 weeks of NC or HFD compared with WT mice (n = 6–14). (D) Genomic Evolutionary Rate Profiling (GERP) of AU-rich elements (AREs) in the FGF21 transcript demonstrates several evolutionarily conserved AREs. The numbers in the legend represent the nucleotide location of the ARE site with respect to the start of the coding region. (E) Fgf21 mRNA is stabilized in primary hepatocytes from lsTtp-KO compared with WT mice (n = 4). (F) TTP protein physically interacts with FGF21 mRNA as assessed by RNA co-IP (n = 3–6). (G) Human FGF21 3′-UTR-luciferase reporter construct signal is higher in Ttp-KO MEFs compared with WT MEFs (n = 6). (H) Overexpression of WT TTP, but not C124R mutant TTP, reduces luminescence signal of the human FGF21 3′-UTR-luciferase reporter construct (n = 5–6). (I) Deletion of ARE in human FGF21 3′-UTR-luciferase construct (ΔARE) abolishes the regulation by TTP overexpression (n = 8–15). Data presented as the relative luciferase activity in the presence of TTP overexpression for each construct. NC, normal chow; HFD, high-fat diet; EV, empty pMIR-REPORT vector; WT, WT human FGF21 3′-UTR-luciferase construct. Data are presented as mean ± SEM. *P < 0.05 by 1-way ANOVA with post hoc Fisher’s LSD test.