The present invention provides antibodies and antigen binding fragments of antibodies that bind to leptin receptor (LEPR) and methods of using the same. According to certain embodiments the invention includes antibodies and antigen binding fragments of antibodies that bind LEPR and activate LEPR signaling. In other embodiments the invention includes antibodies and antigen binding fragments of antibodies that bind to LEPR and enhance sensitization of LEPR to an antigen. In certain embodiments the invention includes antibodies and antigen binding fragments of antibodies that bind LEPR in the presence and absence of leptin. In certain embodiments the invention includes antibodies and antigen binding fragments of antibodies that induce signaling in cells expressing LEPR mutants that otherwise exhibit defective or impaired signaling in the presence of leptin. The antibodies and antigen binding fragments of the present invention are useful for the treatment of lipodystrophies and other diseases and disorders associated with or caused by leptin deficiency or leptin resistance.
