Kategorier: Alle - receptor - therapy - function - structure

af alizee dewilde02 10 år siden

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leptin

Leptin is a cytokine family hormone known for its critical role in regulating food intake, satiety, and body weight. Its structure consists of a monomeric protein with significant sites that facilitate signal transduction and receptor binding.

leptin

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