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Baffled by some of the words? Check out the Key terms page 

Clinical Obesity 

overweight to a degree which causes medical complications

KEY CONCEPT: 

Testing of leptin on patients with clinical obesity and reasons for the failure to control the disease.

Clinical Obesity 

overweight to a degree which causes medical complications

Leptin directly acts on the following; 

 

1) cells of liver and skeletel muscle; here leptin stimulates oxidation of fatty acids which take place in the mitochondria. 

 

As a result of this, there is a reduction of fat in the liver and skeletal muscle (this does not occur in adipose tissue) 

 

MICE which lack leptin do not attain autoimmune diease; there is a possibilty that this could explain reports on how minimizing food intake can assist humans with rheumatoid arthriris 

 

What does Leptin act on? 

Leptin and Obesity 

Mutations which occur either in the gene or the receptor of leptin are scarcely found in obese people 

 

Examples of rare cases:  

Extreme obesity exisiting in 5 members of 2 homoxygous families 

 

OR mutations such as a frameshift in one family and a missense in the other famliy occuring in their leptin gene. 

 

This is similar to the concept of ob/ob mice ; please refer to leptin secretion for more. 

 

people who are hetrozygous - with one normal and one mutant in their leptin genes, acquire moderate obesity. 

 

At the moment, Recombinant human leptin has become available HOWEVER, it is still being tested, to note down whether it will fail to reduce obesity in humans, as it has not been very successful with ob/ob mice. 

 

 

 

 

 

The Case 

However, the 16 September 1999 issue of The New England Journal of Medicine reported the results of a year-long trial of recombinant human leptin in a 9-year-old girl who is homozygous for a frameshift mutation in her leptin genes. The findings:

  • She began the trial weighing 208 pounds (94.4 kg), of which 123 lbs (55.9 kg) was fat (adipose tissue).

  • She was given daily injections of recombinant leptin for one year.

  • At the end of that time,

  • she had lost 36 lbs (16.4 kg), most of it fat.

  • Her appetite and thus food intake had decreased.

  • Her immune system made antileptin antibodies but these did not seem to interfere with the action of the hormone.

But trials of recombinant leptin in obese humans who do not have mutations in both their leptin genes have not shown any great benefit in weight reduction.

 

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