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Adipopnectin regulates the expression of ADAM10 and Notch1 through PPARalpha and JNK pathway respectively. (a) Representative immunoblots and quantification of hippocampal protein levels after chronic ICV injection of AdipoRon, WY14643 (PPARalpha agonist) and GW6471 (PPARalpha antagonist) in 12-month-old mice, including Notch1 and ADAM10. Control, n = 6, AdipoRon, n = 6, WY14643, n = 7, AdipoRon + GW6471, n = 7. *p < 0.05, **p < 0.01, ***p < 0.001 compared with Control, p < 0.05, p < 0.001 compared with AdipoRon treatment. (b) Co-immunoprecipitation results showing chronic ICV injection of AdipoRon or WY14643 enhances the interaction between PPARalpha and RXR. Control, n = 6, AdipoRon, n = 6, WY14643, n = 7. ***p < 0.001 compared with Control. (c) qPCR results showing chronic ICV injection of AdipoRon or WY14643 Induces the recruitment of RXR to the ADAM10 Promoter. Control, n = 6, AdipoRon, n = 7, WY14643, n = 7. ***p < 0.001 compared with Control. (d) Chronic ICV injection of AdipoRon upregulates the activity of JNK. Control, n = 6, AdipoRon, n = 6. ***p < 0.001. (e) Representative immunoblots and quantification of hippocampal protein levels after chronic ICV injection of AdipoRon, Vinblastine (JNK agonist) and SP600125 (JNK antagonist) in 12-month-old mice, including Notch1 and ADAM10. Control, n = 6, AdipoRon, n = 7, Vinblastine, n = 7, AdipoRon + SP600125, n = 7. **p < 0.01, ***p < 0.001 compared with Control, p < 0.001 compared with AdipoRon treatment. Data are presented as means SEM. |