Figure 7. Anti-asprosin mAbs from different sources neutralize asprosin’s orexigenic and glucogenic function by blunting AgRP+ neuronal firing and hepatic cAMP signaling.

(a–f) The anti-asprosin neutralizing antibodies reversibly inhibit asprosin’s effect on AgRP+ neuronal activity. Firing frequency (a, b) and membrane potential (d, e) of AgRP+ neurons were recorded in response to bacterial recombinant asprosin, asprosin preincubated with anti-asprosin rabbit and human mAb, and asprosin after washout. (c, f) Firing frequency response and membrane potential response of AgRP+ neurons were recorded in response to bacterial recombinant asprosin and IgG control antibody. Asterisk (*) indicate the range of alpha as determined by Sidak post hoc test followed by one-way analysis of variance (ANOVA; Figure 7—source data 1). *p<0.05, **p<0.01, ***p<0.001, and ****p<0.0001. (g, h) The anti-asprosin neutralizing antibodies blunt hepatic cAMP signaling. Sixteen-week-old male mice with diet-induced obesity (DIO) were injected with mouse, rabbit, or human mAb against asprosin (250 µg mAb in 500 µl 0.9% saline; n = 8/group). Three hour post-injection, hepatic cAMP levels were measured. Asterisk (*) indicate the range of alpha as determined by the two-tailed Student’s t-test (Figure 7—source data 1). *p<0.05, **p<0.01, ***p<0.001, and ****p<0.0001.