**3. Leptin synthesis**

Effector systems that control energy intake and energy expenditure, hypothalamic control centers where leptin signals from different sources are received, and the size of AT mass are the regulatory steps of leptin synthesis [31]. The major sites of leptin mRNA expression are in the stomach, liver, and AT [32]. Leptin mRNA is also expressed at minor levels in the fetal tissue, placenta, heart, brain, and pituitary gland [18]. Leptin synthesized is generally related to the degree of adiposity. Larger adipocytes express more leptin genes than smaller adipocytes [33]. Mechanical stretching of the fat cell, determined by the amount of stored triglycerides, can generate signals to increase leptin synthesis [24]. In addition, in humans, uridine diphosphate N-acetylglucosamine (UDPGlcNAc) and hexosamine act as potential links between cell size and leptin content. Body mass index is positively correlated with the amount of UDPGlcNAc in subcutaneous AT [34].

The composition of the food, not the amount, affects leptin production [35]. The composition of a meal affects leptin levels; for example, low-fat and high-carb food causes increased leptin levels [36]. Compared to high-carbohydrate meals, high-fat meals lower circulating plasma leptin levels 24 hours after a meal [37]. It has been reported that meals rich in ω-6 polyunsaturated fatty acids (PUFA) increase leptin production [35]. It has been reported that the protein composition of a meal does not affect leptin production [38].

Gender differences have an effect on leptin production. Although there is no difference in leptin levels between girls and boys in the prepubertal period, leptin levels increase in girls and decrease in boys with puberty development [39, 40]. This is explained by the fact that with puberty, the amount of body fat in girls increases more than in boys, and testosterone suppresses leptin levels in boys [41]. In addition, the fact that the subcutaneous AT mass is significantly larger than the omental fat mass of women is also among the factors [39]. Reproductive hormones greatly affect leptin production. Androgenic hormones inhibit leptin synthesis, while estrogens stimulate leptin synthesis [42]. In one study, it was thought that increased estrogen concentrations caused an increase in leptin concentration, which may have been caused by leptin stimulating gonadotrophin releasing hormone (GnRH) synthesis and thus increasing estrogen synthesis [43]. In addition, chronic insomnia and an increase in melatonin concentrations have been reported to decrease plasma leptin concentrations [44].
