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Scientists Find Clue To Safer Obesity Drugs With Fewer Side Effects
Fen-phen was removed from the market more than a decade ago for inducing life-threatening side effects, including heart valve lesions.
Now, the researchers have defined a circuit in the brain that explains the ways fenfluramine, a component of Fen-phen, suppresses appetite.
"Our findings provide evidence that the neural circuit we've proposed is sufficient for the neurotransmitter serotonin to regulate food intake and body weight. Fen-phen works directly on this pathway. Unfortunately, that drug also adversely affects peripheral tissue such as the heart," said Dr. Joel Elmquist, professor of internal medicine and pharmacology at UT Southwestern and senior author of the study.
For the study, the researchers engineered mice in which the expression of a serotonin receptor called 5-hydroxytryptamine 2C was blocked throughout the entire body.
This was previously known to produce obese mice resistant to the anorexic actions of fenfluramine. However, when activated by serotonin, this receptor is also known to suppress appetite.
Using this mouse model, the authors engineered another set of mice in which the same serotonin receptor was blocked everywhere in the body except within a group of brain cells called pro-opiomelanocortin, or POMC, neurons.
The POMC neurons, which are found in the hypothalamus, are also known to play an important role in suppressing appetite and inducing weight loss.
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