Leptin
4 parts :
- Structure
- Receptor
- Function
- Pharmacology

Cytokine family

Monomeric protein

16 kDa

3 important sites

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

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

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

Zhang et al (1994) Positional Cloning of the mouse obese gene and its human homologue. Nature 372 pp425-432

Schwartz et al (2000) Central Nervous System Control of Food Intake. Nature 404 pp661-671

Zhang, Faming, et al. Nature, 1997, 387, 206-209.

Video

https://www.youtube.com/watch?v=G4K6IQZGHJc

Central leptin gene therapy may correct skeletal abnormalities.

Increased femoral length and total bone volume and
Decreased femoral and vertebral cancellous bone volume.

Potential therapeutic for Osteoporosis

Carried out on obese growing mice with leptin-deficiency

Uses of Myalept

Treats generalized lipodystrophy

Subcutaneous Injection

Not suitable for HIV-related Lipodystrophy, or metabolic diseases like diabetes mellitus and hypertriglyceridemia.

Risk of Lymphoma

Leptin may induce neurogenesis and angiogenesis if applied immediately after a stroke.

Leptin is a potent AMPK inhibitor

AMPK inhibits cholestrol synthesis,adipocyte lipogenesis and lipolysis

Increased blood vessels in peri-lesion cortex.

1.5-fold increase in the number of newborn neurons and glia.

Increased expression of leptin receptor and increased phosphorylated AMPK concentration.

Mice was observed to have improved functional states.

6 isoforms(4 found in Human)

II site allows binding with the receptor

Hormone

Body Weight

Food Intake & Satiety

I and III sites transduce the signal

Pharmacokinetics

Half life->3.4h

Elimination->1.3mL/kg/min

Distribution volume->150mL/kg

Secretion

Adipocytes(Main site of secretion)

95% of leptin

Stomach

Leptin secreted by exocrine and endocrine of gastric mucosa

Human placenta

Produced by placental trophoblasts and is secreted into both the maternal and fetal circulation.

Possible link to pregnancy

Plays an essential role in reproduction by regulating gonadotropin-releasing hormone secretion from the hypothalamus.

Leptin production in the placenta is increased in pregnancies complicated with several pathologic conditions.

Renal clearance

Leptin eliminated by kidneys

We are unsure however because we cannot measure elimination through any experimental assays

Obesity is linked to leptin levels