In summary, we report here, for the first time to our knowledge, that: (a) Cardiac FFAR3 promotes inflammation and fibrosis via its classic Gi/o protein signaling, which is opposed by RGS4; (b) Catecholamines negatively modulate cardiac FFAR3 signaling via PKA-mediated RGS4 activation; and (c) RGS4 dampens FFAR3 signaling towards NE release in sympathetic neurons, thereby potentially affording sympatholysis that can help preserve cardiac βAR function, especially in the setting of chronic heart failure. The gene discussed is FFAR3; the disease is congestive heart failure.