The “Fat Gene”

1. The “Fat Gene” Is it possible to cure obesity with a pill?

2. Why study obesity? How does this relate to healthcare? • Nearly 1/3 of Americans are clinically obese. • Almost 2/3 of Americans are considered to be overweight. • These statistics have been on the rise for over the past 100 years. • Obesity is a contributing factor in many diseases including heart disease. • 100’s of millions of dollars have been poured into research by pharmaceutical companies to try to develop a drug to treat obesity.

3. How does this relate to Biotechnology? • In 1994 researchers at Rockefeller University published a paper claiming to have found the “fat” gene. • Since 1994 a multitude of papers on the same gene have also been published. Including a paper in 1995 by the same group that mapped the human “fat” gene to chromosome 7.

4. The ob gene • The gene they found is called the ob (obese) gene. It was first discovered in mice and later in humans.

5. These mice contained a mutation that over-expressed a specific gene. • The original study done on these mice uncovered some interesting information.

6. The obese mice were sterile and prone to sickness • Damage to the hypothalamus caused the same phenotype. • Removal of fat from a mouse caused it to eat more and restore the fat. This led to the coining of the term lipostat. • If fat is removed from a normal mouse and placed in another normal mouse, that mouse will lose the fat.

7. Joining a fat mouse to a normal mouse causes the fat mouse to lose weight. • Proteins from the fat of normal mice can be injected into a fat mouse and cause it to lose weight. • Diabetic mice share the same phenotype as fat mice.

8. Leptin • Researchers were able to determine that the ob gene produces a protein called leptin. • Leptin is believed to control the lipostat of an individual.

9. How does leptin work? • Leptin is secreted by fat cells. • An increase in leptin leads to a decrease in hunger. • A decrease in leptin leads to increased hunger and weight gain. • This works as a feedback loop to control weight gain.

10. Is leptin the answer we have been looking for? • Is it possible to take a pill of leptin to lose weight? NO! • Would leptin injections work? Sometimes. • Gene therapy? Probably not. • We have to realize that only a small percentage (<10%) of the obese population has a mutation in the ob gene.

11. Why were the ob mice sterile? • In order to become reproductive a person has to achieve a certain body mass. Its believed that the level of leptin in their bloodstream plays a role in this.

12. How are ob mice related to diabetic mice? • It was determined several years ago that diabetic mice lack the leptin receptor.

13. Other functions of leptin • Leptin receptors are present in: • The pancrease • Liver • Kidneys • Lungs • Skeletal muscle • This leads researchers to believe that leptin plays a role in many processes inside the body.

14. Leptin plays a role in angiogenesis. • Leptin has been linked to hypertension • Leptin has also been linked to sleep apnea

15. What else is responsible for controlling weight • The brain plays a big role: • There are over 15 different neurotransmitters and enzymes found in the brain besides leptin that regulate appetite suppression and stimulation. • This means that there are over 15 different pathways that regulate your weight. That we know of.

16. What does this mean? • Even though we have discovered the genes that we believe are responsible for obesity, we are not very close to developing a drug to fix/treat them. • The only way to lose weight effectively is to exercise.