Protein: Leptin (Obesity factor) (P50596)
Organism: Rattus norvegicus (Rat)
Function: Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in the activation of several major signaling pathways (By similarity). In the hypothalamus, acts as an appetite-regulating factor that induces a decrease in food intake and an increase in energy consumption by inducing anorexinogenic factors and suppressing orexigenic neuropeptides, also regulates bone mass and secretion of hypothalamo-pituitary-adrenal hormones. In the periphery, increases basal metabolism, influences reproductive function, regulates pancreatic beta-cell function and insulin secretion, is pro-angiogenic for endothelial cell and affects innate and adaptive immunity (By similarity). In the arcuate nucleus of the hypothalamus, activates by depolarization POMC neurons inducing FOS and SOCS3 expression to release anorexigenic peptides and inhibits by hyperpolarization NPY neurons inducing SOCS3 with a consequent reduction on release of orexigenic peptides (By similarity). In addition to its known satiety inducing effect, has a modulatory role in nutrient absorption. In the intestine, reduces glucose absorption by enterocytes by activating PKC and leading to a sequential activation of p38, PI3K and ERK signaling pathways which exerts an inhibitory effect on glucose absorption (By similarity). Acts as a growth factor on certain tissues, through the activation of different signaling pathways increases expression of genes involved in cell cycle regulation such as CCND1, via JAK2-STAT3 pathway, or VEGFA, via MAPK1/3 and PI3K-AKT1 pathways (By similarity). May also play an apoptotic role via JAK2-STAT3 pathway and up-regulation of BIRC5 expression (By similarity). Pro-angiogenic, has mitogenic activity on vascular endothelial cells and plays a role in matrix remodeling by regulating the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). In innate immunity, modulates the activity and function of neutrophils by increasing chemotaxis and the secretion of oxygen radicals. Increases phagocytosis by macrophages and enhances secretion of pro-inflammatory mediators. Increases cytotoxic ability of NK cells (Probable). Plays a pro-inflammatory role, in synergy with IL1B, by inducing NOS2 wich promotes the production of IL6, IL8 and Prostaglandin E2, through a signaling pathway that involves JAK2, PI3K, MAP2K1/MEK1 and MAPK14/p38 (By similarity). In adaptive immunity, promotes the switch of memory T-cells towards T helper-1 cell immune responses (By similarity). Increases CD4(+)CD25(-) T-cell proliferation and reduces autophagy during TCR (T-cell receptor) stimulation, through MTOR signaling pathway activation and BCL2 up-regulation (By similarity).
Subcellular location: Secreted {ECO:0000305|PubMed:25232147}.
Sequence: MCWRPLCRFLWLWSYLSYVQAVPIHKVQDDTKTLIKTIVTRINDISHTQSVSARQRVTGLDFIPGLHPILSLSKMDQTLAVYQQILTSLPSQNVLQIAHDLENLRDLLHLLAFSKSCSLPQTRGLQKPESLDGVLEASLYSTEVVALSRLQGSLQDILQQLDLSPEC
InterPro domains: - IPR000065: Leptin (family) [1-167]
- IPR009079: Four-helical cytokine-like, core (homologous_superfamily) [22-167]
Interaction partners: - Leptin receptor
- Appetite-regulating hormone
- Pro-neuropeptide Y
- 30 kDa adipocyte complement-related protein
- Prolactin
- Prolactin-6A1
- Pro-glucagon
- Erythropoietin
- Granulocyte colony-stimulating factor
- Ciliary neurotrophic factor
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding), GO:0005102 (signaling receptor binding), GO:0005126 (cytokine receptor binding)
Biological Process (BP): GO:0008150 (biological process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0022414 (reproductive process), GO:0000003 (reproduction), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0009605 (response to external stimulus), GO:0048856 (anatomical structure development), GO:0023056 (positive regulation of signaling), GO:1905954 (positive regulation of lipid localization), GO:0042221 (response to chemical), GO:2000241 (regulation of reproductive process), GO:0051240 (positive regulation of multicellular organismal process), GO:0032879 (regulation of localization), GO:0051241 (negative regulation of multicellular organismal process), GO:0051239 (regulation of multicellular organismal process), GO:0051050 (positive regulation of transport), GO:0065008 (regulation of biological quality), GO:0050793 (regulation of developmental process), GO:0044706 (multi-multicellular organism process), GO:0009719 (response to endogenous stimulus), GO:0044703 (multi-organism reproductive process), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0007568 (aging), GO:0048523 (negative regulation of cellular process), GO:0048585 (negative regulation of response to stimulus), GO:0048522 (positive regulation of cellular process), GO:1903530 (regulation of secretion by cell), GO:0051049 (regulation of transport), GO:0051047 (positive regulation of secretion), GO:0032370 (positive regulation of lipid transport), GO:0046887 (positive regulation of hormone secretion), GO:1905952 (regulation of lipid localization), GO:0044057 (regulation of system process), GO:0048513 (animal organ development), GO:0071495 (cellular response to endogenous stimulus), GO:1901700 (response to oxygen-containing compound), GO:0010817 (regulation of hormone levels), GO:0010033 (response to organic substance), GO:0009725 (response to hormone), GO:0046883 (regulation of hormone secretion), GO:0009991 (response to extracellular stimulus), GO:2000026 (regulation of multicellular organismal development), GO:0007565 (female pregnancy), GO:0007584 (response to nutrient), GO:1901698 (response to nitrogen compound), GO:2000833 (positive regulation of steroid hormone secretion), GO:0010646 (regulation of cell communication), GO:0070887 (cellular response to chemical stimulus), GO:0010647 (positive regulation of cell communication), GO:0032098 (regulation of appetite), GO:1905939 (regulation of gonad development), GO:1903532 (positive regulation of secretion by cell), GO:1901652 (response to peptide), GO:0071417 (cellular response to organonitrogen compound), GO:2000831 (regulation of steroid hormone secretion), GO:0032096 (negative regulation of response to food), GO:0071310 (cellular response to organic substance), GO:0002793 (positive regulation of peptide secretion), GO:1901699 (cellular response to nitrogen compound), GO:0044060 (regulation of endocrine process), GO:0032368 (regulation of lipid transport), GO:0043434 (response to peptide hormone), GO:0032870 (cellular response to hormone stimulus), GO:0010243 (response to organonitrogen compound), GO:0031667 (response to nutrient levels), GO:0032105 (negative regulation of response to extracellular stimulus), GO:0051046 (regulation of secretion), GO:0090277 (positive regulation of peptide hormone secretion), GO:2000241 (regulation of reproductive process), GO:0071375 (cellular response to peptide hormone stimulus), GO:1901701 (cellular response to oxygen-containing compound), GO:0071375 (cellular response to peptide hormone stimulus), GO:0032868 (response to insulin), GO:1901653 (cellular response to peptide), GO:0002791 (regulation of peptide secretion), GO:0044320 (cellular response to leptin stimulus), GO:0032869 (cellular response to insulin stimulus)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005576 (extracellular region), GO:0005615 (extracellular space)