Identification
- Generic Name
- Leptin
- DrugBank Accession Number
- DB05098
- Background
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.
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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.
Target Actions Organism ULeptin receptor Not Available Humans - 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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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
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
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
- 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. [Article]
- 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. [Article]
- External Links
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Healthy Subjects (HS) 1 3 Unknown Status Health Services Research Obesity 1 2 Completed Treatment Congenital leptin deficiency / Obesity 1 2 Completed Treatment HIV Lipodystrophy Syndrome 1 2 Completed Treatment Lipodystrophies 1 2 Completed Treatment Obesity 1 1 Completed Treatment Lean / Obese Diabetics / Obesity 1 0 Completed Basic Science Endothelial Dysfunction / Obesity / Vasodilation / Venous Occlusion Plethysmography 1 Not Available Active Not Recruiting Basic Science Obesity 1 Not Available Completed Not Available Healthy Subjects (HS) 1
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 at October 21, 2007 22:23 / Updated at January 14, 2023 19:04