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Symbol LEP contributors: mct/pgu - updated : 12-12-2016
HGNC name leptin
HGNC id 6553
interspecies homolog to murine obese gene (ob)
  • leptin family
  • CATEGORY regulatory , signaling hormone cytokine
    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
    PHYSIOLOGICAL PROCESS behavioral , cardiovascular , digestion , ossification
    metabolism energetic
    signaling hormonal
    a component
    small molecule
  • 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
    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
  • 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
  • ratios of ADIPOQ/LEP and ADIPOQ/RETN constitute novel predictor factors to explain polycystic ovary syndrome (PCOS)
  • Therapy target
    leptin, and potentially PRKAA1 activators, may provide a novel therapeutic approach to AD treatment