Physiological roles of the leptin endocrine system: Differences between mice and humans

Leptin is a 16-kDa cytokine secreted in humans primarily but not exclusivel y by adipose tissues. Its concentration in blood is usually proportional to body fat mass, but is higher in women than in men not only because of a di fferent distribution of and greater fat mass in women, but also because tes tosterone reduces its level in men. Leptin features in different ways durin g the life span. It is synthesized in the ovary, transported in the oocyte, and made by both fetus and placenta, particularly during the last month of gestation. It is made by the lactating mammary gland and ingested by the n ewborn infant in its milk. The prime importance of leptin is realized at pu berty when it is necessary for progression to a normal adult reproductive s tatus in females. Fasting and chronic undernutrition result in a lower leve l of leptin in the blood. Lack of leptin results in hunger, ensuring that t he individual eat to survive, and also inhibition of reproduction, until su ch time as food and fat stores are adequate to supply energy for pregnancy and lactation. Thus, leptin is important for survival of the individual and survival of the species. Although an extremely rare genetic absence of lep tin induces hyperphagia and obesity in humans, as it does in mice, there ap pears to be little role for leptin in humans in ensuring that fat stores ar e not in excess of adequate, that is, in preventing obesity. The mouse diff ers from humans in many respects, in particular in the far more drastic way s it conserves energy when it very rapidly adapts to lack of food. These in clude not only suppression of reproduction but also lowering of its body te mperature (torpor), suppressing its thyroid function, suppressing its growt h, and increasing secretion of stress hormones (from the adrenal). This rev iew concentrates on roles of leptin in human physiology and pathophysiology but also discusses why some observations on actions of leptin in mice are not applicable to humans.