Leptin
4 parts :
- Structure
- Receptor
- Function
- Pharmacology
Pharmacology
Obesity is linked to leptin levels
Renal clearance
Leptin eliminated by kidneys
We are unsure however because we cannot measure elimination through any experimental assays
Secretion
Human placenta
Produced by placental trophoblasts and is secreted into both the maternal and fetal circulation.
Possible link to pregnancy
Leptin production in the placenta is increased in pregnancies complicated with several pathologic conditions.
Plays an essential role in reproduction by regulating gonadotropin-releasing hormone secretion from the hypothalamus.
Stomach
Leptin secreted by exocrine and endocrine of gastric mucosa
Adipocytes(Main site of secretion)
95% of leptin
Pharmacokinetics
Distribution volume->150mL/kg
Elimination->1.3mL/kg/min
Half life->3.4h
Function
I and III sites transduce the signal
Food Intake & Satiety
Body Weight
Hormone
Receptor(LEPR)
II site allows binding with the receptor
6 isoforms(4 found in Human)
Current Prospects &
Conclusion
Leptin may induce neurogenesis and angiogenesis if applied immediately after a stroke.
Increased expression of leptin receptor and increased phosphorylated AMPK concentration.
Mice was observed to have improved functional states.
1.5-fold increase in the number of newborn neurons and glia.
Increased blood vessels in peri-lesion cortex.
Leptin is a potent AMPK inhibitor
AMPK inhibits cholestrol synthesis,adipocyte lipogenesis and lipolysis
Uses of Myalept
Risk of Lymphoma
Not suitable for HIV-related Lipodystrophy, or metabolic diseases like diabetes mellitus and hypertriglyceridemia.
Subcutaneous Injection
Treats generalized lipodystrophy
Central leptin gene therapy may correct skeletal abnormalities.
Carried out on obese growing mice with leptin-deficiency
Increased femoral length and total bone volume and
Decreased femoral and vertebral cancellous bone volume.
Potential therapeutic for Osteoporosis
References
Video
https://www.youtube.com/watch?v=G4K6IQZGHJc
Zhang, Faming, et al. Nature, 1997, 387, 206-209.
Schwartz et al (2000) Central Nervous System Control of Food Intake. Nature 404 pp661-671
Zhang et al (1994) Positional Cloning of the mouse obese gene and its human homologue. Nature 372 pp425-432
Philippe G. Cammisotto , Diane Gingras , Christian Renaud , Emile Levy , Moïse Bendayan
American Journal of Physiology - Gastrointestinal and Liver PhysiologyPublished 1 February 2006Vol. 290no. 2, G242-G249DOI: 10.1152/ajpgi.00334.2005
Avraham, Y., Davidi, N., Lassri, V., Vorobiev, L., Kabesa, M., Dayan, M., Chernoguz, D., Berry, E., Leker, R. R., (2011) 'Leptin Induces Neuroprotection, Neurogenesis and Angiogenesis after Stroke', Current Neurovascular Research, Vol 8, No.4, November, pp. 313-322
Iwaniec, U.T, Boghossian, S., Lapke, P.D, Turner, R.T, Kalra, S.P., (2007) 'Central Leptin Gene Therapy Corrects Skeletal Abnormalities in Leptin-Deficient ob/ob Mice', Peptides, Vol 28, No.5, May, pp. 1012-1019
Structure
3 important sites
Monomeric protein
16 kDa
4 alpha helix and 2 anti-parallel beta pleated sheets
1 disulfide bond
Cytokine family
