PL
Leptin is an adipose tissue-derived hormone whose circulating levels correlate with the amount of body fat stores. The main function of this adipokine is to regulate energy metabolism. By modulating the expression of orexigenic and anorexigenic neuropeptides in the hypothalamus, leptin reduces appetite. It also increases energy expenditure, contributing to the decrease of body fat and body weight. Mutations in the leptin receptor gene or prolonged consumption of a high-fat diet may impair leptin action, leading to leptin resistance. Resistance to leptin can also be an adaptive response that occurs in seasonal animals and in pregnant mammals. Reversible insensitivity to the satiety signal of leptin promotes hyperphagia, which is essential for animals living in dynamic environments and experiencing seasonal variation in food availability, since it allows them to forage intensely when food is abundant and accumulate fat reserves necessary to survive periods when food is scarce. Moreover, leptin resistance and subsequent hyperphagia develop during pregnancy in order to meet the energy needs of the growing fetus. Physiological leptin resistance may be due to impaired transport of leptin across the blood-brain barrier and/or to decreased sensitivity of the hypothalamus to this hormone resulting from an inhibition of leptin signalling in hypothalamic neurons. In pregnancy, an increased resistance to leptin action is also mediated by the binding of this adipokine to its placenta-derived soluble receptor. Reduced entry of leptin into the brain as well as alterations in the leptin signalling pathway in the hypothalamus leads to a transient decrease in sensitivity to this hormone preventing appetite suppression.