**2. Leptin synthesis and regulation**

Leptin derives from adipose tissue's obese gene (OB) transcription product [6]. The OB gene function was first identified in the *ob/ob* obese mice model and is located on chromosome 7 (7q31.3) and has three exons and two introns (18 kb) [7, 8]. Leptin receptors are located on chromosome 1 (1p31) and are noted with 17 introns and 18 exons and encode two proteins of 166 and 1162 amino acids, respectively [9]. Leptin receptors are highly expressed in the hypothalamus, cerebellum, and other tissues associated with the vasculature, stomach, and placental organs [10]. Leptin receptors have five spliced isoforms, the longest form expressed in neuronal tissue and the short forms expressed almost in all tissue types [11]. Leptin receptors (OB-R) are structurally similar to the class I cytokine family receptors. Alternative splicing of leptin receptor RNA results in various isoforms, designated as OB-Ra, OB-Rb, OB-Rc, OB-Rd, OB-Re, and OB-Rf. They all have an extracellular domain of more than 800 amino acids, a transmembrane domain of 34 amino acids, and a variable intracellular domain. The pleiotropic biological effects of leptin are explained based on the wide distribution of leptin receptors in humans [5]. Leptin bind to its hypothalamic receptors (Ob-Rs) in the brain and activates appetite and satiety. The concentration of leptin in plasma depends on the person's dietary behavior, gender, and physical activities. The other

hormonal constituents, such as insulin, estrogen, and glucocorticoids, can also influence the regulation mode and the level of leptin in the blood [12, 13]. On the other hand, low energy or fasting, thyroid hormones, androgens, inflammatory cytokines, and adrenergic agonists can inhibit leptin secretion [14].
