Identification

Name
Leptin
Accession Number
DB05098
Description

Although leptin is a circulating signal that reduces appetite, in general, obese people have an unusually high circulating concentration of leptin. These people are said to be resistant to the effects of leptin, in much the same way that people with type 2 diabetes are resistant to the effects of insulin. Thus, obesity develops when people take in more energy than they use over a prolonged period of time, and this excess food intake is not driven by hunger signals, occurring in spite of the anti-appetite signals from circulating leptin. The high sustained concentrations of leptin from the enlarged fat stores result in the cells that respond to leptin becoming desensitized.

Type
Small Molecule
Groups
Investigational
Synonyms
Not Available

Pharmacology

Indication

Investigated for use/treatment in lipodystrophy and obesity.

Contraindications & Blackbox Warnings
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Pharmacodynamics
Not Available
Mechanism of action

It is unknown whether leptin can cross the blood-brain barrier to access receptor neurons, because the blood-brain barrier is somewhat absent in the area of the median eminence, close to where the NPY neurons of the arcuate nucleus are. If it does cross the blood-brain barrier, it is unknown whether this occurs via an active or passive process. It is generally thought that leptin might enter the brain at the choroid plexus, where there is intense expression of a form of leptin receptor molecule that might act as a transport mechanism.

Once leptin has bound to the Ob-Rb receptor, it activates the molecule stat3, which is phosphorylated and travels to the nucleus, it is presumed, to effect changes in gene expression. One of the main effects on gene expression is the down-regulation of the expression of endocannabinoids, responsible—among their many other functions—for increasing appetite. There are other intracellular pathways activated by leptin, but less is known about how they function in this system. Neuronal receptors remodel in response to leptin to have a different number and different types of synapses.

Although leptin is a circulating signal that reduces appetite, in general, obese people have an unusually high circulating concentration of leptin.[3] These people are said to be resistant to the effects of leptin, in much the same way that people with type 2 diabetes are resistant to the effects of insulin. Thus, obesity develops when people take in more energy than they use over a prolonged period of time, and this excess food intake is not driven by hunger signals, occurring in spite of the anti-appetite signals from circulating leptin. The high sustained concentrations of leptin from the enlarged fat stores result in the cells that respond to leptin becoming desensitized.

In mice, leptin is also required for male and female fertility. In mammals generally, and in humans in particular, puberty in females is linked to a critical level of body fat. When fat levels fall below this threshold (as in anorexia), the ovarian cycle stops and females stop menstruating.

Leptin is also strongly linked with angiogenesis, increasing VEGF levels.

TargetActionsOrganism
ULeptin receptorNot AvailableHumans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half-life

24.9+/-4.4 min

Clearance
Not Available
Adverse Effects
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Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

Products

Categories

Drug Categories
Classification
Not classified

Chemical Identifiers

UNII
Q09SXY6BFI
CAS number
169494-85-3
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

References

General References
  1. de Luis DA, Sagrado MG, Conde R, Aller R, Izaola O: Changes of ghrelin and leptin in response to hypocaloric diet in obese patients. Nutrition. 2008 Feb;24(2):162-6. doi: 10.1016/j.nut.2007.11.001. [PubMed:18165128]
  2. van de Wall E, Leshan R, Xu AW, Balthasar N, Coppari R, Liu SM, Jo YH, MacKenzie RG, Allison DB, Dun NJ, Elmquist J, Lowell BB, Barsh GS, de Luca C, Myers MG Jr, Schwartz GJ, Chua SC Jr: Collective and individual functions of leptin receptor modulated neurons controlling metabolism and ingestion. Endocrinology. 2008 Apr;149(4):1773-85. Epub 2007 Dec 27. [PubMed:18162515]
PubChem Substance
347909945
RxNav
1441651
Wikipedia
Leptin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentHealthy Volunteers1
3RecruitingHealth Services ResearchBMI >30 kg/m21
2Active Not RecruitingTreatmentBMI >30 kg/m21
2CompletedTreatmentBMI >30 kg/m21
2CompletedTreatmentBMI >30 kg/m2 / Leptin Deficiency1
2CompletedTreatmentHIV Lipodystrophy1
2CompletedTreatmentLipodystrophies1
1CompletedTreatmentLean / Obese / Obese Diabetics1
0CompletedBasic ScienceBMI >30 kg/m2 / Endothelial Dysfunction / Vasodilation / Venous Occlusion Plethysmography1
Not AvailableCompletedNot AvailableHealthy Volunteers1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
Not Available
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Transmembrane signaling receptor activity
Specific Function
Receptor for obesity factor (leptin). On ligand binding, mediates signaling through JAK2/STAT3. Involved in the regulation of fat metabolism and, in a hematopoietic pathway, required for normal lym...
Gene Name
LEPR
Uniprot ID
P48357
Uniprot Name
Leptin receptor
Molecular Weight
132492.66 Da

Drug created on October 21, 2007 16:23 / Updated on June 12, 2020 10:52

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