1. LEP: The Leptin Gene and Its Correlation to Obesity
Lindsay Camm
March 8, 2007

2. The LEP Gene
The leptin gene, LEP, is found in humans on the 7th chromosome.
Homologous to the OB gene in mice
Controversial gene with some evidence that its mutation causes obesity

3. LEP Gene Structure Three exons separated by two introns
20 kilobases long
First intron and exon occur at the 5’ untranslated region
Second exon codes for 48 amino acids
Third exon occurs in the coding region and 3’ untranslated region and codes for 118 or 119 amino acids

4. LEP Gene Structure Cont...
Two different cDNA encode the leptin protein
The leptin protein can either be 166 or 167 amino acids long
If an internal alternative splice adds glutamine +49, the protein will have 167 AA’s

5. Chromosomal Assignment of the LEP Gene
Staining of metaphase chromosomes with propidium iodide has shown that homologous chromosomes 7 have the same twin-spot signals that are found on an isolated LEP gene

6. LEP Function Produces the 167 amino acid protein leptin
When adipose cells grow due to increased food uptake, leptin is released and sent to the hypothalamus
Leptin regulates appetite and stimulates the release of hormones involved in reproduction
It sends a satiety signal, inhibiting food intake and stimulating energy expenditure

7. Leptin’s Mechanism

8. Why is evidence of a LEP mutation important?
Obesity is a major epidemic, effecting 32.9% of Americans
It is a predisposing factor to the leading causes of death including heart disease, high blood pressure, stroke, diabetes, and some cancers
If we can understand ALL of the causes of obesity, including the genetic factor, we can work to prevent this disease

9. LEP Gene Mutations Autosomal recessive frameshift mutation
Leptin gene mutations cause a significant decrease in leptin production
Most current research has found that leptin secretion deficiencies rarely cause obesity
HOWEVER, some studies on homozygous gene mutations show incidence of morbid obesity

10. The Research Says...
Most obese individuals studied showed no mutation in the LEP gene or leptin levels
A significant number of subjects studied who were heterozygous for the mutation were moderately obese
Extremely inbred families studied who were homozygous for the mutation had decreased leptin levels, were morbidly obese, and had sexual immaturity

11. In order to see an increase in body mass due to decreased leptin levels, a person must be homozygous for the mutation

12. Research in Mice
There is more research and conclusive evidence that mutation in the OB gene in mice leads to obesity
The OB gene was first discovered in mice in 1950, before the discovery of the human homologue
The structure of the OB gene in mice is almost identical to the LEP gene in humans

13. Therapy
Treatment for individuals with the homozygous mutation involves leptin injections
Since the gene cannot adequately produce leptin, the protein must be injected into the bloodstream
Studies conducted in mice showed that after two weeks of leptin treatments, the body weight of the mice decreased by 30%

14. Results of Leptin Treatment in Mice with and without the OB gene mutation

15. Conclusion
The LEP gene in humans and corresponding OB gene in mice produces leptin, a protein regulating appetite and reproduction
Evidence that a mutation of this gene causes obesity is controversial
Research on this possible genetic predisposal to obesity is currently very popular in order to find more treatments for morbid obesity
While there is no substitute for healthy diet and exercise, other auxiliary treatments like leptin injections may be beneficial in fighting obesity