Human Leptin (gene name OB) is a 16 kDa, 146 amino acid (aa) residue, non-glycosylated polypeptide that regulates adipose tissue mass and energy balance . Mature human Leptin shares 87% and 84% aa identity with mouse and rat Leptin, respectively. Human Leptin is active in both the mouse and rat systems . Leptin is expressed almost exclusively by adipocytes and its production is influenced by hormones, cytokines and nutrients and circulates in the plasma, crosses the blood-brain barrier, and is present in human breast milk . The human Leptin receptor (designated ObR or LEPR) is a 150 kDa, 1144 aa residue, type I transmembrane glycoprotein of the IL-6 receptor family of Class I cytokine receptors . The gene for ObR undergoes considerable splicing, forming variants a-d with cytoplasmic domains of variable length, plus the potentially soluble form ObRe . The long form, ObRb (formerly OB RL), is expressed mainly in the hypothalamic arcuate nucleus and is essential for signal transduction . In a concentration-dependent manner, Leptin signaling can have diverse effects, causing neurons that express pro-opiomelanocortin (POMC) peptides to reduce food intake, and neurons that express neuropeptide Y and agouti-related protein (NpY and AgRP) to increase food intake . Leptin is fundamentally a Â?starvation signalÂ? that, when low, prompts increased appetite and decreased energy expenditure . Leptin deficiency influences the immune system, depressing Th1 responses and causing increased frequency of infections . Leptin also regulates puberty, blocking the onset of puberty, or of menses if Leptin deficiency exists due to excessive thinness, such as results from starvation, extreme exercise-induced weight loss, anorexia or cancer-induced cachexia .
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