The present invention relates, in part, to agents for binding and/or inactivating native ghrelin. These agents include those that specifically bind and/or cleave octanoylated native ghrelin. Such agents include antibodies and enzymes. The agents also include those that can be used to generate antibodies that specifically bind and/or cleave octanoylated native ghrelin. Compositions that include the agents are also provided. Further provided are methods of producing and using the agents and compositions thereof. For instance, the agents and compositions can be used to reduce or eliminate the hunger response activity of octanoylated native ghrelin. Therefore, the agents, compositions and methods provided can be used to suppress appetite and/or treat obesity. In addition, the agents, compositions and methods can be used to treat any disease associated with or caused by ghrelin (e.g., Prader-Willi Syndrome).