Leptin is a mainly adipocyte-secreted protein that was discovered 5 years ago. Most of the research following this discovery focused on the role of leptin in body weight regulation, aiming to illuminate the pathophysiology of human obesity. However, more and more data are emerging that leptin is not only important in the regulation of food intake and energy balance, but that it also has a function as a metabolic and neuroendocrine hormone. It is now clear that it is especially involved in glucose metabolism, as well as in normal sexual maturation and reproduction. Besides this, interactions with the hypothalamic±pituitary±adrenal, thyroid and GH axes and even with haematopoiesis and the immune system have also been described. It has been shown that leptin secretion by the adipocyte is partly regulated by other hormones, such as insulin, cortisol, and sex steroids, mainly testosterone. Also, other hormones like thyroid hormone and GH are possibly involved in leptin synthesis. Leptin itself exerts effects on different endocrine axes, mainly on the hypothalamic±pituitary±gonadal axis and on insulin metabolism, but also on the hypothalamic±pituitary±adrenal, thyroid and GH axes.Leptin may thus be considered a new endocrine mediator, besides its obvious role in body weight regulation.

ABSTRACT. Background. Leptin, the protein product of the ob gene, is produced by the adipocyte and seems to function as a link between adiposity, satiety, and activity. Leptin has also been found to be necessary for pubertal development, conception, and pregnancy in mice, and is increased in prepubertal children, independent of adiposity, suggesting a role in childhood growth and development. This study investigated 100 mother/newborn pairs to determine the role of leptin in neonatal development. Placental tissue was assayed for leptin mRNA to evaluate it as a source of leptin production in utero.Methods. One hundred mother/newborn pairs were enrolled in this study. Radioimmunoassay was performed for leptin on maternal venous and newborn cord blood. Leptin concentrations were measured in 43 children in Tanner stages 1 and 2 as a control group. Placental tissue was obtained from five mothers and assayed for leptin mRNA by reverse transcription/polymerase chain reaction (RT/PCR). Human placental cell lines JAR and JEG-3 were also assayed for leptin mRNA expression.Results. Leptin was present in all newborns studied at a mean concentration of 8.8 ng/mL (؎9.6 standard deviations). Leptin concentrations in cord blood correlated with newborn weight (r ‫؍‬ .51), body mass index (BMI) (r ‫؍‬ .48), and arm fat (r ‫؍‬ .42). There was no correlation between leptin and insulin. When statistically covarying for adiposity for newborns and Tanner stages 1 and 2 children, newborns had greater concentrations of leptin (mean, 10.57 ng/mL) than children (mean, 3.04 ng/mL). Leptin was present in all mothers at a mean value of 28.8 ng/mL (؎22.2 standard deviations). Leptin concentration correlated with prepregnancy BMI (r ‫؍‬ .56), BMI at time of delivery (r ‫؍‬ .74), and arm fat (r ‫؍‬ .73). Maternal leptin correlated with serum insulin (r ‫؍‬ .49). There was no correlation between maternal and newborn leptin concentrations. Thirteen percent of newborns had higher leptin concentrations than their mothers. Placental tissue from five separate placentas expressed leptin mRNA at comparable or greater levels than adipose tissue. Two human trophoblastic placental cell lines, JAR and JEG-3, also expressed leptin mRNA. Conclusions.The correlation between leptin and adiposity found in children and adults was also found in newborns. Serum leptin concentrations in newborns were increased more than three-fold compared with children in Tanner stages 1 and 2 when controlling for adiposity, suggesting that leptin concentrations in the newborn are not explained by adiposity alone. Maternal leptin concentrations correlated with measures of adiposity at delivery but did not correlate with newborn adiposity or leptin. Leptin mRNA was expressed both in placental tissue and in two human placental cell lines. These data suggest that leptin has a role in intrauterine and neonatal development and that the placenta provides a source of leptin for the growing fetus. Pediatrics 1997; 100(1). URL: http://www.pediatrics.org/cgi/content/full/ 100/1/e1; leptin, ...

As one of the postulated roles of the ob gene product, leptin, is regulation of energy balance and preservation of normal body composition, we investigated the effect of acute and chronic calorie excess (weight gain) on serum leptin in humans. Two protocols were employed: 1) acute (12-h) massive (120 Cal/kg) voluntary overfeeding of eight healthy individuals; and 2) chronic overfeeding to attain 10% weight gain, with its subsequent maintenance for additional 2 weeks, involving six normal males. In the acute experiments (protocol 1), circulating leptin rose by 40% over baseline (P < 0.01) during the final hours of overfeeding; this increase persisted until the next morning. At the point of achievement and the 2-week maintenance of 10% weight gain (protocol 2), a more than 3-fold rise in the basal leptin concentration was observed (P < 0.01). A direct linear relationship was found between the magnitude of the leptin response to weight gain and the percent gain of body fat (r = 0.88; P < 0.01). In summary, 1) in contrast to normal food intake (8), short term massive overfeeding is associated with a moderate elevation of circulating leptin levels that persists until next feeding cycle is initiated; and 2) a 10% weight gain causes different changes in the body composition, and the resulting rise in circulating leptin parallels the increase in the percentage of body fat. In conclusion, these studies document acute elevation of leptin in response to positive energy balance and suggest that developing resistance to leptin is associated with bigger fat deposition during weight gain in humans.

Since the discovery of leptin, a boom of scienti®c knowledge became available about the OB-protein gene and its role and signi®cance in weight regulation. Both from animal and human research data, serum leptin can probably be considered as one of the best biological markers to re¯ect total body fat, and this ®nding is true over a wide range of body mass indexes (BMIs) and in different pathologies: in normal weight, anorexic and obese subjects; in non insulindependent diabetes mellitus (NIDDM) patients, PCO women, Prader-Willi children and subjects with hypogonadism and growth hormone de®ciency.Gender differences clearly exist, probably related to sex hormone differences, and from fat distribution studies it could be shown that subcutaneous fat is much more related to serum leptin concentrations than visceral fat: also leptin messenger-RNA (m-RNA) expression is signi®cantly higher in subcutaneous fat from human obese subjects.Leptin is not only correlated to a series of endocrine parameters such as insulin, insulin-like growth factor, (IGF) and SHBG, it seems involved as a mediator in some endocrine mechanisms (onset of puberty, insulin secretion, etc) as well.Weight loss will reduce human leptin concentrations, whereas the administration of human recombinant leptin seems to show only limited effects.Keywords: leptin; body fat distribution; endocrinology; hormones IntroductionObesity is becoming a major health problem in western countries, with an annual growing incidence and its association with increased morbidity and mortality. Furthermore, obesity is a very complex problem in its development, being a multifactorial disease, as well as in its treatment. Knowledge of the mechanisms by which obesity develops can help in prevention and better treatment. The discovery of leptin 1 and the subsequent wealth of research on the subject, has already led to more insight into these mechanisms. 2 Evidence from the research until now points out that leptin is likely to be a crucial hormone in the regulation of body weight, in humans as well as in animal models. 2 It is clear that leptin plays an important role in the regulation of body weight, more speci®cally of body fat stores. Almost all studies hitherto found a strong relationship between leptin and weight, expressed as body mass index (BMI) or percent body fat. 2 ± 4 But for a certain BMI, a large variability in leptin levels is found. 2,3,5 Also manifest differences in leptin concentration between men and women have been found by different authors. 6,7 Given the close interrelationships between body weight, body fat distribution and many hormonal functions, in energy balance regulation, leptin may play an important and triggering role as a hormonal determinant of energy balance in addition to the well-known role played by insulin, catecholamines, glucagon 8 and thyroid hormones. 9 As it is a fact that leptin and its receptor are two important components of a homeostatic system regulating body fat, it is likely that the process of leptin's signalling by the hypothalam...