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Leptin (Molecule of the Month for October 2002)

Appetite represing hormone

The World Health Organization has now classified obesity as a disease. It is often said that obesity is the biggest health problem facing the developed world today. It causes health problems such as hypertension, type II diabetes, heart attacks and strokes, elevated cholesterol and many more. Obesity is said to lead to 30,000 premature deaths each year and it is shortening the lives of people by an average of nine years.

Redux, in the 1980's which sold 2 million prescriptions within the first 6 months of its launch in the US and which went on to be sold in 65 countries suppressed the appetite. However it was eventually taken off the market because of the effects it had on the heart. There are now only 2 drugs on the market in the UK- Xenical, which slows absorption of fat and Reductil, which suppresses the appetite. Both of these are prescription drugs, can have side affects and can only reduce weight slightly.

Several hormones are responsible for our eating habits. For example; Leptin and alpha-MSH are both appetite represent. Cannaboids, neuropeptide Y, ghrelin and anandamid are all feeding stimulants.

One of the hormones being researched for this reducing weight is Leptin. Leptin is an appetite suppressant. It stops you eating too much as well as makes you more active so you burn off more energy.

It is produced by a specific gene found in fat cells called the obese(ob) gene. Small amounts of leptin are also secreted by cells in the epithelium, stomach and placenta. The amount of Leptin found in people increases as their body fat increases. There is also a higher concentration of mRNA in fat from obese compared to thin subjects. Leptin acts on receptors in the hypothalamus of the where it: The theory is that as you get fatter you also get less sensitive to the affects of Leptin. Leptin works on the body in the following ways;

  • counteracts the effects of neuropeptide Y(feeding stimulant secreted by cells in the gut wall and in the hypothalmus);
  • counteracts the affects of anandamid(another feeding stimulant that binds to the same receptors as THC the active ingredient of marijuana)
  • promotes the effects of alpha-MSH a appetite represent;
  • resulting in inhibition of food intake
  • it also stimulates secretion of reproductive hormones such as gonadotrophin-releasing hormone and thus leutenizing and follicle stimulating hormone from the anterior pituitary.
  • it raises the temperature of the subject so energy expenditure is increased
Leptin also acts directly on the cells of the liver and skeletal muscles where it stimulates the oxidation of fatty acids in the mitochondria. This reduces the storage of fat in those tissues (but not in adipose[fat] tissue). Leptin receptors are also present in T lymphocytes.

In rare cases the gene that produces leptin or its receptors mutate. This can cause severe obesity and diabetes in certain individuals as well as in certain cases failure to reach puberty. However most people who are obese do not have a defective ob gene.

Leptin of humans has 146 amino acid sequence containing one disulphide bond.Its molecular weight is around 16 kDa. Leptin has 67% sequence identity among diverse species.

Leptin is a four-helix bundle with one very short strand segment and two relatively long interconnected loops. This is consistent with a classification as a cytokine four-helix bundle.

Picture of Leptin 3D model

click on the picture of  Leptin above to interact
with the 3D model of the
Leptin structure
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Picture of Leptin

Update by karl harrison
(Molecule of the Month for October 2002 )

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