It had been shown that adipose tissue secreted some unknown factor that influenced appetite. However, the importance of adipose tissue as an endocrine organ was only fully appreciated in 1994 with the discovery of Leptin, the protein product of the Ob gene. Leptin is a strong appetite suppressant that, when deleted, causes an obese phenotype in mice. The discovery of leptin, and its effects on appetite, led to hopes of a treatment for type 2 diabetes and obesity, a major disease in the developed world. It has since been discovered that the brain can become resistant to leptin, even at supra-physiological levels, making treatment with leptin impossible. Nonetheless, intense interest in the existence of adipose derived hormones has since led to the discovery of numerous important protein hormones, and the full appreciation of adipose tissue as an important endocrine organ.