Leptin, also known as OB, is a polypeptide hormone that regulates adipose tissue mass and energy balance. In mice (ob/ob) and humans, inactivating mutations of the OB gene can cause obesity. Leptin signals through the transmembrane Leptin R in the hypothalamus but can also bind shorter and soluble forms of Leptin R which do not signal. Adipocytes increase Leptin expression as cell size increases, resulting in depressed appetite and increased energy expenditure. Low Leptin levels prompt increased appetite and decreased energy expenditure. Leptin can also block the onset of puberty or menses during starvation, extreme exercise-induced weight loss, anorexia, or cancer-induced cachexia.