Leptin is a hormone secreted from white adipocytes and plays important role in the regulation of food intake and energy balance. Leptin functions via signaling pathways involving OB-R in hypothalamus. Animal models have revealed the influence of Leptin in reducing body weight and regulating blood glucose level. When mutations are introduced in obese gene, mice with impaired function of leptin are massively obese and in high risk of diabetes. Leptin deficiency reduces metablic rate. Leptin deficient mice are less active and with lower body temperature than normal animals. Human Leptin shares approximately 84% sequence identity with the mouse protein. Human Leptin consists of 167 amino acid residue including a 21 amino acid residue signal sequence and 146 amino acid residue mature protein sequence.
Leptin is one of the most important hormones secreted by adipocytes, as an adipokine that modulates multiple functions including energy homeostasis, thermoregulation, bone metabolism, endocrine, and pro-inflammatory immune responses. The circulating leptin levels serve as a gauge of energy stores, thereby directing the regulation of energy homeostasis, neuroendocrine function, and metabolism. Recent studies suggest that leptin is physiologically more important as an indicator of energy deficiency, rather than energy excess, and may mediate adaptation by driving increased food intake and directing neuroendocrine function to converse energy, such as inducing hypothalamic hypogonadism to prevent fertilization. One of these functions is the connection between nutritional status and immune competence. The adipocyte-derived hormone Leptin has been shown to regulate the immune response, innate, and adaptive response, both in normal and pathological conditions,. Thus, Leptin is a mediator of the inflammatory response. Leptin has a dual effect on bone, acting by two independent mechanisms. As a signal molecule with growth factor characteristics, leptin can stimulate osteoblastic cells and inhibit osteoclast formation and activity, thus promoting osteogenesis. However, as a molecule that stimulates sympathetic neurons in the hypothalamus, leptin indirectly inhibits bone formation. This inhibitory effect of leptin mediated by activation of the sympathetic nervous system can be abrogated by the application of blood pressure-reducing beta-blockers, which also inhibit receptors of hypothalamic adrenergic neurons. Leptin appears to regulate some features defining Alzheimer's disease (AD) at the molecular and physiological level. Leptin can stimulate mitogenic and angiogenic processes in peripheral organs. Because leptin levels are elevated in obese individuals and excess body weight has been shown to increase breast cancer risk in postmenopausal women. Furthermore, a recent report clearly shows that targeting leptin signaling may reduce mammary carcinogenesis.
Leukocyte-Associated Immunoglobulin-Like Receptor 1 (LAIR1) is a single-pass type I membrane protein. LAIR1 expressed on the majority of peripheral mononuclear cells, including natural killer (NK) cells, T-cells, B-cells, monocytes, and dendritic cells, highly in naive T-cells and B-cells. As an inhibitory receptor, LAIR1 plays a constitutive negative regulatory role on cytolytic function of natural killer (NK) cells, B-cells and T-cells. Activation by Tyr phosphorylation results in recruitment and activation of the phosphatases PTPN6 and PTPN11. It also reduces the increase of intracellular calcium evoked by B-cell receptor ligation. LAIR1 plays inhibitory role independently of SH2-containing phosphatases and modulates cytokine production in CD4+ T-cells. It down-regulates IL2 and IFNG production while inducing secretion of transforming growth factor beta, also down-regulates IgG and IgE production in B-cells as well as IL8, IL10 and TNF secretion. LAIR1 inhibits the differentiation of peripheral blood precursors towards dendritic cells. It also restrains proliferation and induces apoptosis in myeloid leukemia cell lines as well as prevents nuclear translocation of NF-kappa-B p65 subunit/RELA and phosphorylation of I-kappa-B alpha/CHUK in these cells.
Leukocyte-Associated Immunoglobulin-Like Receptor 2 (LAIR2) is a secreted, 131 amino acid protein that contains one Ig-like C2 type domain, making it a member of the Ig superfamily. When compared to LAIR-1, its transmembrane counterpart, it shares 83% amino acid identity across the signal sequence and extracellular domains; although one is secreted and one is membrane-bound, the two LAIR proteins are thought to have arisen from a common gene ancestor and appear to share similar adhesion profiles. This suggests that LAIR-2 may compete with LAIR-1 for ligand binding. A 114 amino acid alternate splice form of LAIR-2 is truncated at the C terminus, but retains the entire Ig domain. The expression profile of these splice forms, and the presence of orthologs in other species, have not been reported.
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