Importantly, we observed a complete lack of FGF21-induced SHP2 phosphorylation in TG WAT. SHP2, when phosphorylated on Y542, couples FGF-induced FRS signaling to Grb2 binding and MAPK activation [26]. Despite our observation of increased FRS phosphorylation (Figure 3B), this did not correlate with increased SHP2 phosphorylation (Figure 3C). It is worth mentioning that FGF21 and leptin pathways possibly converge on SHP2 [27]. Since SHP2 is also activated in response to leptin-induced signaling, it will be worthwhile to investigate if leptin and FGF21 co-operate for typical MAPK activation.
