The hungry fetus? Role of leptin as a nutritional signal before birth


Corresponding author A. J. Forhead: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK. Email:


In adult animals, leptin is an adipose-derived hormone that is important primarily in the regulation of energy balance during short- and long-term changes in nutritional state. Expression of leptin and its receptors is widespread in fetal and placental tissues, although the role of leptin as a nutritional signal in utero is unclear. Before birth, leptin concentration correlates with several indices of fetal growth, and may be an endocrine marker of fetal size and energy stores in the control of metabolism and maturation of fetal tissues. In addition, leptin synthesis and plasma concentration can be modified by insulin, glucocorticoids, thyroid hormones and oxygen availability in utero, and therefore, leptin may be part of the hormonal response to changes in the intrauterine environment. Evidence is emerging to show that leptin has actions before birth that are tissue-specific and may occur in critical periods of development. Some of these actions are involved in the growth and development of the fetus and others have long-term consequences for the control of energy balance in adult life.