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The “Fat Gene” Is it possible to cure obesity with a pill? 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. 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. The ob gene The gene they found is called the ob (obese) gene. It was first discovered in mice and later in humans. These mice contained a mutation that over-expressed a specific gene. The original study done on these mice uncovered some interesting information. 1) 2) 3) 4) 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. 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. 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. 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. 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. 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. How are ob mice related to diabetic mice? It was determined several years ago that diabetic mice lack the leptin receptor. 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. Leptin plays a role in angiogenesis. Leptin has been linked to hypertension Leptin has also been linked to sleep apnea 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. 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.