Metreleptin was approved by the Japanese Ministry of Health, Labor and Welfare in March 2013 for the treatment of lipodystrophy and by the US FDA in February 2014 for the treatment of generalized lipodystrophy. Metreleptin is a recombinant N-methionyl analog of the leptin protein; leptin itself was identified via positional cloning in studies on the cause of obesity in the ob/ob mouse strain, which lacks the leptin gene. While there have been many studies of leptin in obesity, this first approval of a leptin analog is directed toward the treatment of lipodystrophy. Toward that end, the effects of leptin administration were studied in a transgenic mouse model of lipodystrophy (with constitutive activation of sterol-regulatory-element-binding-protein- 1c) that results in lack of white adipose tissue. Since, adipocytes serve as a storage depot for triglycerides (TG), the lack of adipocytes results in ectopic lipid deposition in organs such as liver causing hepatomegaly and severe insulin resistance.
