**1.2 Leptin**

Leptin is a 16 kDa protein product of the ob gene located on chromosome 1p31 and was identified in 1994 [1]. The name "leptin" comes from the Greek word "leptos," which means "thin," because this protein causes increased energy expenditure and reduces calorie intake by acting on satiety signals in the hypothalamus [26]. Its amino acid sequence exhibits no major homologies to other proteins [27] and it's made by differentiated adipocytes, but it's also made in other tissues like the stomach fundus, skeletal muscle, the liver, and the placenta [28]. Leptin suppresses food intake and increases energy expenditure by acting on the hypothalamus [29]. It is also a pro-inflammatory protein and a member of the IL-6 super-family of cytokines [30]. Leptin enhances insulin sensitivity in the periphery and regulates pancreatic β-cell activity [13]. Despite a functioning leptin receptor and high leptin levels, leptin does not cause weight loss in the majority of cases of obesity. This reduced response to the anorexigenic and insulin-sensitizing effects of leptin is called "leptin resistance" [13].

During pregnancy, leptin modulates gonadotrophin-releasing hormone release and facilitates implantation [31]. It also boosts amino acid uptake, regulates placental growth, enhances mitogenesis, and induces human chorionic gonadotrophin synthesis in trophoblast cells [31]. Tumor necrosis factor (TNF) and interleukin (IL)-6 stimulate the synthesis of placental leptin mRNA [32]. Leptin levels begin to rise in the early stages of pregnancy, regardless of maternal weight gain [33], peaking approximately 28 weeks of pregnancy and then dropping to pre-gravid levels shortly after delivery [34]. The placenta, rather than maternal adipose tissue alone, appears to play a significant role in the rise in maternal leptin concentrations throughout pregnancy [35]. The presence of a distinct promoter region in the human placental leptin gene indicates that placental leptin is regulated differently from adiposederived leptin [36]. The fetus itself contributes to leptin production starting early in the second trimester [37]. In comparison to the placenta, however, the fetus produces a modest amount of it. Furthermore, leptin concentrations in umbilical cord plasma correlate positively with birth weight of newborns [38].

Leptin levels are higher in pregnant women with PE [23] and they may be higher before the disease manifests itself clinically [39, 40], with peaks occurring around 28 weeks of gestation [34]. As a result, leptin may play a role in the disease's pathogenesis. However, other authors have observed lowered [25] or unchanged [41] circulating levels in patients with PE.
