Using Hormones to Induce Weight-loss
Revisiting Recombinant Leptin As a Way to Loose Weight
Jan 30, 2009
Leptin is a hormone naturally found in the body that lets the brain know that there is fat on the body. In response to leptin the brain suppresses appetite and weight loss is induced. Concentrations of leptin in the blood are directly related to the amount of fat on the body. In some obese children who were having a hard time losing weight, it was found that they were missing the gene that made leptin. In their case the brain was not getting the message about the fat on the body, therefore not suppressing the children’s appetite.
Leptin as a Weight Loss Drug
The discovery of the role of leptin in weight-loss opened new doors into the treatment of obesity. The theory was that if an overweight person was given leptin, it could trick the body into suppressing appetite, increasing energy expenditure and losing weight. Leptin worked great in the lab animals but when translated to obese humans, it was another story. It turns out that most obese people have developed resistance to the effects of leptin. The brain does not get the message about the fat, so appetite increases, energy is conserved and weight loss does not occur.
Weight Loss Drugs That Chaperone Leptin
In a recent study, researchers used chemical chaperones to re-sensitize the brain effectively to responding to leptin (Lale Ozcan et al., “Endoplasmic Reticulum Stress Plays a Central Role in Development of Leptin Resistance” Cell Metabolism, Volume 9, Issue 1, 35-51, 7 January 2009). The study used mice with reduced leptin sensitivity. When the mice were pretreated with the chaperones 4-PBA (Buphenyl) or TUDCA (tauroursodeoxycholic acid), leptin sensitivity increased. The mice then demonstrated weight loss even when fed a high fat diet. Both chaperones are Food and Drug Administration approved drugs but for other uses.
Drugs That Increase Sensitivity to Leptin
Orexin allows the body to utilize leptin more efficiently. Orexin is a natural chemical found in the brain. Scientists are hoping to develop a drug that mimics orexin. When high levels of orexin are found in the brain of lab animals, they do not gain weight when fed a high fat diet. (Hiromasa Funato et. Al., “Enhanced Orexin Receptor-2 Signaling Prevents Diet-Induced Obesity and Improves Leptin Sensitivity” Cell Metabolism, Volume 9, Issue 1, 64-76, 7 January 2009). The introduction of orexin into the brain of an overweight person can help obese people regain their sensitivity to leptin which will result in weight loss.
How Overweight People Can Be a Part of the Drug Development Process
The best way to be a part of the drug investigation process is to participate in a clinical trial. This is a way for people to take a more active role in their health care. Clinical trials give people an "in" on treatments before the treatments become commonly available. As a study participant, people receive excellent medical care from top-notch healthcare facilities and providers. Trial participants also get the chance to help others by being a part of the cure discovery process.
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