leptin

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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