Leptin controls the production of C-Reactive Protein (CRP), which, in turn, interacts with leptin to diminish its ability to signal satiety and reduce food intake. The interactions between leptin and CRP can be exploited to screen for agents capable of disrupting the leptin-CRP interaction, and thereby improve leptin signaling. Such agents can be used to reduce body weight, adiposity, and alleviate insulin resistance and diabetes.