Heart arrhythmia is associated with metabolic diseases. Drosophila melanogaster has proven to be an excellent model to study the correlation between heart arrhythmia and metabolic defects. We used high-fat diet (HFD)-fed flies to investigate its metabolic effect on heart function and found that HFD increased the heartbeat and induced arrhythmia. HFD up-regulated the expression of Adipokinetic hormone (Akh), the functional equivalent of human glucagon. Down-regulating Akh in the Akh producing cells (APCs) rescued the heart defects caused by HFD. Furthermore, we found that the Akh receptor, AkhR, mediates the pathogenic effects of HFD on the heart. Strikingly, two neurons, which are located in the posterior abdomen and are closely associated with the heart, expressed high levels of AkhR. These two neurons form synapses on the heart muscles and control the heartbeat. This finding of an APC-heart axis and the cardiac neurons paves the way for further investigation into heartbeat and heart arrhythmia using Drosophila.