LEP gene encodes a protein that is secreted by white adipocytes, which plays a major role in the regulation of body weight. This protein, which acts through the leptin receptor, functions as part of a signaling pathway that can inhibit food intake or regulate energy expenditure to maintain constancy of the adipose mass. This protein has several endocrine functions, and is involved in the regulation of immune and inflammatory responses, angiogenesis, hematopoiesis and wound healing. Mutations in this gene cause severe obesity, and morbid obesity with hypogonadism. This gene is also linked to type 2 diabetes mellitus development. LEP gene is located from base pair 128,241,188 to base pair 128,257,628 on chromosome 7. The structure of leptin consists of a complex four helices, similar to that of cytokines. Leptin is produced by the white adipose tissue, the most frequent form of adipose tissue in mammals. The white adipose tissue provides a long-term fuel reserve that can be mobilized during food deprivation with the release of fatty acids for oxidation in other organs; it also provides thermal insulation and has a mechanical role for vital organs. Leptin is produced in many sites in addition to white adipose tissue, but the amount of body fat is the main determinant of the circulating levels of this hormone. After it is produced, leptin is secreted into the bloodstream, where it circulates attached to proteins, and is transported to the brain, where it stimulates or inhibits release of several neurotransmitters. It down-regulates some orexigenic neuropeptides, such as the neuropeptide Y, melanin concentrating hormone, orexins, and agouti-related peptide. Leptin up-regulates anorexigenic neuropeptides such as alpha-melanocyte-stimulating hormone, which acts on the melanocortin-4 receptor, cocaine and amphetamine-regulated transcripts, and corticotropin-releasing-hormone. Leptin may also directly affect the metabolism and function of peripheral tissues such as the adipocytes, skeletal muscle, ovary, adrenal cortex, and pancreatic beta cells.
Last date updated on September, 2014