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FLASH GENE
Symbol LEP contributors: mct/pgu - updated : 12-12-2016
HGNC name leptin
HGNC id 6553
PROTEIN
PHYSICAL PROPERTIES Hydrophobic
STRUCTURE
motifs/domains
HOMOLOGY
interspecies homolog to murine obese gene (ob)
Homologene
FAMILY
  • leptin family
  • CATEGORY regulatory , signaling hormone cytokine
    SUBCELLULAR LOCALIZATION extracellular
    text secreted by adipocytes
    basic FUNCTION
  • controlling the size of adipose depot by a profound effect of appetite and energy expenditure and regulating bone formation and bone remodeling via the sympathetic nervous system
  • involved in control of the hypothalamic-pituitary-gonadal (HPG) axis, during the development of the hypothalamus, and a neonatal critical period, preceding leptin acute regulation of food intake in adults
  • also putative angiogenic factor, playing a key role in metabolic syndrome especially in obese children
  • having proinflammatory and prothrombotic effects that could link increased adipose mass directly to atherogenesis
  • can be involved in the pathomechanism of atherosclerotic plaque formation also through its effect on cholesterol biosynthesis in monocytes
  • playing a role in blood pressure independently of obesity, and in the reproductive axis
  • acting, in part, by inhibiting the synthesis of NPY and its release from the hypothalamus
  • modulate neural activation in key striatal regions, suggesting that the hormone acts on neural circuits
  • governing food intake to diminish the perception of food reward while enhancing the response to satiety signals generated during food consumption
  • playing a role in the pathophysiological course of cholelithiasis
  • with LIF, CNTF, IL6, participate to the complex control of the reproductive function by affecting the development and function of the hypothalamus-pituitary system at different ontogenic times and anatomical sites
  • might significantly contribute to the production of major gel-forming mucins by direct stimulation of airway epithelial cells
  • by separately regulating EGR1 activation and synthesis, CCK and LEP interact cooperatively to define the capacity for satiety signaling by vagal afferent neurons
  • LEP, RETN, TNF may have differentiating roles in the pathogenesis of Systemic sclerosis (SSc)
  • GHRL, and LEP play an important role in the maintenance of the balance of IL17-producing and T-regulatory cells during pregnancy
  • defective central leptin signalling and impaired leptin entry into the CNS (central nervous system) represent two important aspects of leptin resistance in obesity
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS behavioral , cardiovascular , digestion , ossification
    PATHWAY
    metabolism energetic
    signaling hormonal
    HPG
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • SIGLEC6
  • binding to CRP and attenuating its physiological functions (contributing to leptin resistance and to increased adiposity)
  • interacting with PRKAA1 (activates PRKAA1 in skeletal muscle but inhibits PRKAA1 in the hypothalamus and may also act independently of PRKAA1, through PI3K as shown in hippocampal neurons)
  • TNF, IL6, and leptin, which have been implicated in insulin sensitivity regulation, regulate the expression of STEAP4
  • interacting with CCK and EGR1
  • GABBR1 subunit is constitutively expressed by adipocytes to primarily regulate LEP expression at the transcriptional level through a mechanism not relevant to the function as a partner of heterodimeric assembly to the functional GABBR1
  • chronic elevation of CRP observed in obese subjects may worsen LEP resistance, contributing to the pathogenesis of cardiovascular disease
  • LEP promotes fetal lung maturity and upregulates SFPTA1 expression in pulmonary alveoli type-II epithelial cells involving TTF1 activation
  • LEP plays an important role in mitochondrial function and insulin sensitivity in the hypothalamus by regulating HSPD1
  • CRP can impede the access of leptin to the CNS, and elevation of CRP within the CNS can have a negative impact on the physiological actions of leptin
  • cell & other
  • can interact with stimuli related to the visual appearance and the recent ingestion of food to modulate spontaneous eating behavior
  • REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) OBS1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in Alzheimer disease (AD) patients, and serum levels are inversely correlated to severity of dementia
    constitutional     --over  
    in placentas of preeclampsia and HELLP syndrome
    Susceptibility
  • to obesity
  • common promoter variant associated with changes in the relationship between serum leptin and fat mass in obese girls
  • Variant & Polymorphism SNP
  • 2548 G>A and others
  • obese carriers of common allelic variations had an increased risk to display extreme snacking behavior
  • Candidate gene
    Marker
  • ratios of ADIPOQ/LEP and ADIPOQ/RETN constitute novel predictor factors to explain polycystic ovary syndrome (PCOS)
  • Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerativealzheimer
    leptin, and potentially PRKAA1 activators, may provide a novel therapeutic approach to AD treatment
    ANIMAL & CELL MODELS