LEP
Leptin (from Greek λεπτός leptos, "thin") is a hormone predominantly made by adipose cells and enterocytes in the small intestine that helps to regulate energy balance by inhibiting hunger, which in turn diminishes fat storage in adipocytes.
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 (PubMed:17344214, PubMed:15899045, PubMed:19688109).
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) (PubMed:8589726, PubMed:11460888, PubMed:19688109, PubMed:24340098, PubMed:25060689).
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 (PubMed:24340098).
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) (PubMed:17344214).
May also play an apoptotic role via JAK2-STAT3 pathway and up-regulation of BIRC5 expression (PubMed:18242580).
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) (PubMed:11460888).
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 (PubMed:12504075).
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 (PubMed:15899045, PubMed:19688109).
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 (PubMed:25060689).
Biological Process
Activation of protein kinase C activityManual Assertion Based On ExperimentIDA:UniProtKB
Adipose tissue developmentIEA:Ensembl
Adult feeding behaviorISS:HGNC-UCL
AngiogenesisManual Assertion Based On ExperimentIDA:UniProtKB
Aorta developmentIEA:Ensembl
Bile acid metabolic processIEA:Ensembl
Bone growthISS:UniProtKB
Bone mineralization involved in bone maturationIEA:Ensembl
Cardiac muscle hypertrophyIEA:Ensembl
Cellular response to insulin stimulusIEA:Ensembl
Cellular response to L-ascorbic acidIEA:Ensembl
Cellular response to leptin stimulusManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to retinoic acidIEA:Ensembl
Central nervous system neuron developmentIEA:Ensembl
Cholesterol metabolic processIEA:Ensembl
Circadian rhythmIEA:Ensembl
Determination of adult lifespanIEA:Ensembl
Eating behaviorIEA:Ensembl
Elastin metabolic processIEA:Ensembl
Energy reserve metabolic processManual Assertion Based On ExperimentIBA:GO_Central
Fatty acid beta-oxidationIEA:Ensembl
Female pregnancyIEA:Ensembl
Glucose homeostasisIEA:Ensembl
Glucose metabolic processIEA:Ensembl
Glycerol biosynthetic processIEA:Ensembl
Hormone metabolic processIEA:Ensembl
Insulin secretionIEA:Ensembl
Intestinal absorptionManual Assertion Based On ExperimentIDA:UniProtKB
Intracellular signal transductionIEA:Ensembl
Leptin-mediated signaling pathwayISS:UniProtKB
Leukocyte tethering or rollingIEA:Ensembl
Lipid metabolic processManual Assertion Based On ExperimentIBA:GO_Central
Negative regulation of apoptotic processIEA:Ensembl
Negative regulation of appetiteISS:HGNC-UCL
Negative regulation of appetite by leptin-mediated signaling pathwayISS:UniProtKB
Negative regulation of autophagyManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of cartilage developmentIEA:Ensembl
Negative regulation of glucagon secretionIEA:Ensembl
Negative regulation of glucose importManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of glutamine transportIEA:Ensembl
Negative regulation of lipid storageIEA:Ensembl
Negative regulation of transcription by RNA polymerase IIIEA:Ensembl
Negative regulation of vasoconstrictionIEA:Ensembl
Ovulation from ovarian follicleIEA:Ensembl
PhagocytosisIEA:Ensembl
Placenta developmentManual Assertion Based On ExperimentIDA:DFLAT
Positive regulation of cold-induced thermogenesisBy SimilarityISS:YuBioLab
Positive regulation of developmental growthManual Assertion Based On ExperimentIDA:DFLAT
Positive regulation of fat cell apoptotic processIEA:Ensembl
Positive regulation of follicle-stimulating hormone secretionIEA:Ensembl
Positive regulation of hepatic stellate cell activationIEA:Ensembl
Positive regulation of insulin receptor signaling pathwayIEA:Ensembl
Positive regulation of interleukin-12 productionIEA:Ensembl
Positive regulation of interleukin-6 productionManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of interleukin-8 productionManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of ion transportIEA:Ensembl
Positive regulation of luteinizing hormone secretionIEA:Ensembl
Positive regulation of MAPK cascadeManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of p38MAPK cascadeManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of peroxisome proliferator activated receptor signaling pathwayIEA:Ensembl
Positive regulation of phosphatidylinositol 3-kinase signalingManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of protein import into nucleusIEA:Ensembl
Positive regulation of protein kinase B signalingISS:UniProtKB
Positive regulation of protein phosphorylationManual Assertion Based On ExperimentIDA:ARUK-UCL
Positive regulation of reactive oxygen species metabolic processIEA:Ensembl
Positive regulation of receptor signaling pathway via JAK-STATManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of T cell proliferationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of TOR signalingManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of tumor necrosis factor productionIEA:Ensembl
Positive regulation of tyrosine phosphorylation of STAT proteinIEA:Ensembl
Prostaglandin secretionManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of angiogenesisManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of blood pressureIEA:Ensembl
Regulation of bone remodelingISS:UniProtKB
Regulation of brown fat cell differentiationISS:UniProtKB
Regulation of cell cycleManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of cytokine production involved in inflammatory responseManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of endothelial cell proliferationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of gluconeogenesisIEA:Ensembl
Regulation of insulin secretionIEA:Ensembl
Regulation of intestinal cholesterol absorptionIEA:Ensembl
Regulation of lipoprotein lipid oxidationIEA:Ensembl
Regulation of natural killer cell activationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of natural killer cell mediated cytotoxicityManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of natural killer cell proliferationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of nitric-oxide synthase activityManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of steroid biosynthetic processIEA:Ensembl
Response to activityIEA:Ensembl
Response to dietary excessIEA:Ensembl
Response to estradiolIEA:Ensembl
Response to ethanolIEA:Ensembl
Response to hypoxiaIEA:Ensembl
Response to insulinManual Assertion Based On ExperimentIBA:GO_Central
Response to vitamin EIEA:Ensembl
Sexual reproductionManual Assertion Based On ExperimentIMP:UniProtKB
T cell differentiationISS:UniProtKB
Tyrosine phosphorylation of STAT proteinManual Assertion Based On ExperimentIBA:GO_Central
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