Status
Please wait ...

Details for messenger / hormone: leptin

EndoNet ID: ENH00160

To link to the content of EndoNet use the EndoNet ID that is given on the detail pages in the format ENX0000, where X is a place holder for the type of the component (e. g. R for receptor or C for anatomical structure).
As URL for the linking append this ID to the detail page for this type of component.
For an hormone that would be:

http://endonet.bioinf.med.uni-goettingen.de/hormone/ENH00000

It is also possible to use the search of EndoNet to link to the right detail page. The URL should look like

http://endonet.bioinf.med.uni-goettingen.de/search/ENC00000
If the search pattern is unambigious the user is directed to the corresponding detail page.

Synonyms

  • leptin
  • OB
  • obese protein
  • obesity factor
  • LEP

General information

  • Leptin is an adipose tissue-derived secretory hormone that suppresses appetite by inhibition of neuropepeptide Y (NPY) gene expression in arcuate nucleus (ARC) in the hypothalamus. [1]
  • Other negative regulators include catecholamines, androgens, cAMP agonists, β-adrenergic receptor agonists, phorbol esters and possibly thyroid hormone. [2]
  • Disease: obesity; it is associated with high circulating leptin concentration. [3]
  • A 16-kDa protein secreted primarily from adipocytes. [4]
  • Inhibits feeding, enhances energy expenditure, and stimulates gonadotropes. [5]
  • Leptin stimulates fatty acid oxidation by activating 5'-activated AMP kinase (AMPK) in muscle. [6]
  • Leptin can repress stearoyl CoA desaturase through a central pathway. [6]
  • Leptin inhibits hepatic triglyceride accumulation by activating phosphatidylinositol-3-kinase. [6]
  • In humans, the half-life of leptin is about 75 minutes. [7]
  • Product of the ob gene. [6]
  • Leptin inhibits neurons that increase food intake including those expressing NPY and AGRP and potentiates neurons that reduce food intake including neurons expressing POMC. [8]
  • Leptin reduces hyperphagia, increases glucose metabolism, decreases glycogen content, stimulates fatty acid oxidation, inhibits insulin secretion, stimulates proliferation of CD4+ T lymphocytes and increases production of cytokines, accelerates maturation of reproductive organs. [2]
  • Leptin directly stimulates fatty acid oxidation through the activation of AMP-dependent protein kinase and subsequent inhibition of acetylCoA carboxylase. [2]
  • Increased levels of intracellular glucosamine (a by-product of increased glucose uptake) enhance leptin production in both adipocytes and skeletal muscle. [2]
  • TNF alpha, insulin, endothelin-1 and glucocorticosteroids are reported to increase leptin production in white adipocytes. [2]
  • Leptin reduces food intake by upregulating anorexigenic (appetite-reducing) neuropeptides, such as alpha-melanocyte-stimulating hormone, and downregulating orexigenic (appetite-stimulating) factors, primarily neuropeptide Y. [9]
  • Leptin and insulin are major signals to the hypothalamus to regulate energy homoeostasis and body adiposity. IR (insulin receptors) and leptin receptors (long isoform, ObRb) share a number of signalling cascades, such as JAK2/STAT-3 (Janus kinase 2/signal transduction and activator of transcription 3) and PI3K (phosphoinositide 3-kinase); the cross-talk between IR and ObRb have been described previously in non-neuronal cells. [10]
  • Leptin is secreted by adipose tissue in proportion to fat mass. [11]
  • Can mimic some of the insulin actions in liver, adipose tissue, and muscle. [4]
  • Human leptin levels are pulsatile and inversely related to pituitary-adrenal function. [12]
  • Leptin and insulin share common intracellular signal transduction pathways in rat hypothalamus: there is a convergence of leptin and insulin signaling at the level of IRSs-PI 3-kinase and a divergence at the level of Akt. [13]
  • The transporter system of leptin through the blood-brain barrier is mediated by the short form of the leptin receptor (LRa), a protein expressed in the choroid plexus that acts to transport leptin into the cerebrospinal fluid. [14]
  • Leptin upregulates collagen expression in hepatic stellate cells. [15]
  • Insulin-sensitizing thiazolidinediones repress leptin gene expression through the activation of PPARγ. [2]
  • The presence of functional leptin receptors in brains regions and peripheral organs that are important in cardiovascular control such as heart, kidneys and adrenals led to suspect that leptin played a key role in blood pressure control. [16]

Classification

Hormone function

  • metabolism
    • cell metabolism
      • nutrient supply

      Chemical classification

      • hormone
        • genome-encoded
          • cytokines
            • Leptin family

        Composition

        Sequence
        VPIQKVQDD TKTLIKTIV TRINDISHT 
        QSVSSKQKV TGLDFIPGL HPILTLSKM 
        DQTLAVYQQ ILTSMPSRN VIQISNDLE 
        NLRDLLHVL AFSKSCHLP WASGLETLD 
        SLGGVLEAS GYSTEVVAL SRLQGSLQD 
        MLWQLDLSP GC
        UniProt P41159

        Links to other resources

        UniProt P41159
        Ensembl ENST00000308868
        KEGG hsa:3952
        • Anatomical structure: adipose_tissue

          • The majority of Leptin is expressed in white adipose tissue while a small amount is present in brown adipose tissue. [2]

          Influenced by:

          • melanocortin-4 receptor
            in adipose_tissue
            • Leptin secretion and gene expression of differentiated rat adipocytes is inhibited by administration of alpha-MSH (alpha-melanocyte stimulating hormone), and this effect is antagonised by antagonist of melanocortin receptor MC4R (AgRP, agouti-related protein). [17]
          • PPARgamma1
            in adipose_tissue
            • Catecholamines (beta 2 adrenoreceptor), cAMP agonists, and peroxisome proliferator-activated receptor gamma (PPAR-gamma) inhibit leptin synthesis and secretion. [18]
          • beta-2 adrenoreceptor
            in adipose_tissue
            • Catecholamines (beta 2 adrenoreceptor), cAMP agonists, and peroxisome proliferator-activated receptor gamma (PPAR-gamma) inhibit leptin synthesis and secretion. [18]
          • galanin receptor 1
            in adipose_tissue
            • Galanin inhibits ob gene expression and leptin protein secretion in vitro and in vivo. [18]
            • Galanin-induced decrease in plasma level of leptin might be mediated by inhibiting leptin release from pre-existing intracellular pool. [18]
            • Inhibitory action of galanin probably involved in GalR1 signaling, galanin-repressed leptin production may be mediated by changes in intracellular cAMP level. [18]
          • leptin receptor
            in adipose_tissue
            • Leptin receptor is involved in regualting the circulating leptin concentration. [19]
            • Tonic suppression of leptin synthesis could be mediated by effects of leptin on the adipocyte leptin receptor acting in an autocrine fashion. [19]
          • leptin receptor isoform b
            in adipose_tissue
            • Isoform b from leptin receptor is responsible for mediating the autoregulation of leptin expression in adipose tissue. [19]
            • Leptin receptor mediated autocrine suppression by leptin on its own expression in adipose tissue is likely to play an important role in regulating plasma leptin concentration. [19]
          • TNFR1
            in adipose_tissue
            • Leptin secretion is regulated by TNF-alpha posttranslationally. This secretagogue-like activity is consistent with the existence of regulatable pools of leptin and may contribute in part to the insulin resistance properties of TNF-alpha as well as the adipostatic mechanisms of leptin. [20]
          • TNFR2
            in adipose_tissue
            • Leptin secretion is regulated by TNF-alpha posttranslationally. This secretagogue-like activity is consistent with the existence of regulatable pools of leptin and may contribute in part to the insulin resistance properties of TNF-alpha as well as the adipostatic mechanisms of leptin. [20]
        • Anatomical structure: fat_cell

          Influenced by:

          • growth hormone receptor
            in fat_cell
          • insulin receptor
            in fat_cell
          • beta-1 adrenoreceptor
            in fat_cell
            • Catecholamines suppress leptin release from in vitro differentiated subcutaneous human adipocytes via b1- and b2-adrenergic receptors. [21]
          • beta-2 adrenoreceptor
            in fat_cell
            • Catecholamines suppress leptin release from in vitro differentiated subcutaneous human adipocytes via b1- and b2-adrenergic receptors. [21]
        • Anatomical structure: cell_of_endometrium_of_uterus

          • Endometrial leptin secretion is regulated in vitro by the human blastocyst. [22]
        • Anatomical structure: mucosa_of_gastric_wall

          • A low level of leptin may be produced in gastric epithelium, placenta and skeletal muscle. [2]
        • Anatomical structure: placenta

          • A low level of leptin may be produced in gastric epithelium, placenta and skeletal muscle. [2]
          • Leptin is secreted by placenta. [23]

          Influenced by:

          • ER-alpha
            in placenta
            • Estradiol upregulates leptin expression in placental cells. This effect probably involves both genomic and nongenomic actions via crosstalk between ER alpha and MAPK and PI3K signal transduction pathways. [24]
        • Anatomical structure: skeleton_muscle

          • A low level of leptin may be produced in gastric epithelium, placenta and skeletal muscle. [2]
        • Anatomical structure: fat_cell_of_brown_fat

          Influenced by:

          • PRLR
            in fat_cell_of_brown_fat
            • Prolactin combined with insulin significantly increases leptin expression and release from differentiated brown adipocytes, indicating that prolactin potentiates the stimulatory effect of insulin as revealed by the recruitment of insulin receptor substrates and the activation of phosphatidylinositol 3-kinase. [25]
            • Prolactin is not directly involved in transcription rate, but more likely in the secretion or release process of leptin in vivo. [25]

        Targets

        Cellleptin receptorleptin receptor isoform b
        acidophil somatotroph cell of anterior pituitary Present
        Influences
        • GH
        adipose tissue Present
        Phenotypes
        • negative regulation of insulin receptor signaling pathway
        • regulation of glucose homeostasis
        • negative regulation of gene expression
        • insulin resistance
        • hyperinsulinemia
        • obesity
        Influences
        • leptin
        • insulin
        Present
        Influences
        • leptin
        arcuate nucleus of hypothalamus Present
        Phenotypes
        • regulation of synapse organization
        Influences
        • alpha-MSH
        • AGRP
        • NPY
        • POMC
        • GnRH-I
        cell of endometrium of uterus Present
        Influences
        • IL-1 beta
        continuous vascular endothelial cell of blood vessels and lymphatics Present
        Influences
        • endothelin-1
        fat cell Present
        Phenotypes
        • regulation of lipid metabolic process
        Present
        Influences
        • ANG-2
        granulosa cell Present
        Phenotypes
        • negative regulation of steroid hormone biosynthetic
        heart Present
        Phenotypes
        • regulation of cardiac myocyte metabolism
        hepatocyte Present
        Phenotypes
        • negative regulation of insulin receptor signaling pathway
        hypothalamus Present
        Influences
        • orexin-B
        • orexin-A
        kidney Present
        Phenotypes
        • positive regulation of diuresis by pressure natriuresis
        pancreas Present
        Phenotypes
        • non-insulin-dependent diabetes mellitus (NIDDM)
        Influences
        • insulin
        paraventricular nucleus of hypothalamus Present
        Influences
        • TRH
        • CRH
        • norepinephrine
        peritoneal mesothelial cell Present
        Influences
        • TGF-beta 1
        placenta Present
        Phenotypes
        • trophoblast cell proliferation
        preadipocyte Present
        Influences
        • VEGF-165
        skeleton muscle Present
        Phenotypes
        • positive regulation of fatty acid oxidation
        T-lymphocyte Present
        Phenotypes
        • positive regulation of T cell activation
        theca cell Present
        Phenotypes
        • negative regulation of steroid hormone biosynthetic
        vascularendothelial cell Present
        Phenotypes
        • positive regulation of vasodilation
        Reference