It is often said that ‘The way to a man's heart is through his stomach’, and, although the original author of this quote is unknown, I bet he/she was an endocrinologist – someone who understood that many of the hormones that communicate the sensations of hunger and thirst in our bodies can also modify our heartbeat. New on the list of such appetite-altering hormones is Nesfatin-1, a potent appetite-suppressing hormone found in mammals that was recently ascribed an additional role in cardiac regulation when researchers at the University of Calabria, Italy, demonstrated that it reduces the pressure generated by the left ventricle of rat hearts. As Nesfatin-1 is known to be an anorexic agent in other vertebrates, like the goldfish, the Italian team wanted to know whether the hormone could similarly play on a fish's heartstrings.
To get to the heart of the matter, the team began by isolating goldfish hearts and then connecting them, separately, to a series of tubes to allow each heart to pump saline solution through its chambers just as if it was pumping blood inside a fish. Next, they added Nesfatin-1 to the fluid perfusing the hearts to see whether the hormone changed the volume and pressure of saline ejected from the heart during a heartbeat (stroke volume and stroke work, respectively). The team found that even small amounts of Nesfatin-1 increased both the stroke volume and stroke work of the hearts, meaning that Nesfatin-1 stimulates goldfish hearts to increase performance – which is the opposite of the effect described in mammals. To confirm the specificity of this response, the team then perfused the hearts with a combination of Nesfatin-1 and its specific inhibitor and found that, as expected, the function of the hearts decreased back to initial resting levels.
Confident that Nesfatin-1 is indeed a cardiac regulating hormone in fish, the team began probing the underlying mechanism by which this hormone sets the goldfish heart aflutter. They perfused their isolated goldfish hearts with various combinations of Nesfatin-1 and specific pharmacological inhibitors that target discrete steps in intracellular signaling pathways to see which drugs blocked the stimulating effects of Nesfatin-1. With this approach, the team identified several key players in Nesfatin-1 signaling in heart muscle cells, beginning with adenylate cyclase activation, which causes a rise in intracellular cyclic AMP and subsequent activation of protein kinase A – an enzyme that phosphorylates specific proteins to rapidly modify their function. Protein kinase A then targets several muscle proteins to ultimately facilitate the rapid cycling of calcium ions that is essential for cardiac contraction.
Together, the Italian team provides a thorough account of the action and process of Nesfatin-1 signaling in goldfish hearts, showing us that this appetite-altering hormone is also at the heart of the endocrine regulation of cardiac function in goldfish.