A single gene mutation stops neurons from sending appetite suppressing signals to the right part of the brain, resulting in uncontrolled gluttony and subsequent obesity, scientists from Georgetown University Medical Center reported in the journal Nature Medicine. The authors explained that their findings could lead to ways of turning on brain sensitivity to insulin and leptin, hormones that suppress appetite – for example, there might be a way of stimulating expression of that faulty gene.
The researchers found that the mutation in the Bdnf (brain-derived neurotrophic factor) gene undermines brain neurons’ ability to pass insulin and leptin chemical signals through the brain. Their study involved mice.
When a human being has eaten, leptin and insulin are released into the body and literally tell the body to stop consuming food. However, if the signals do not reach parts of the brain they are supposed to – within the hypothalamus – the person will continue feeling hungry, and will carry on eating.
Baoji Xu, Ph.D., said:
“This is the first time protein synthesis in dendrites, tree-like extensions of neurons, has been found to be critical for control of weight. This discovery may open up novel strategies to help the brain control body weight.”
Dr. Xu has been carrying out research on the Bdnf gene for years. He explains that this gene produces a growth factor that regulates how neurons communicate with each other.
Xu has demonstrated that during development, BDNF plays a major role in the formation and maturity of synapses. A synapse is the point where two nerve cells connect; a specialized junction at which a neuron (nerve cell) communicates with a target cell – this is done via chemical signals. The Bdnf gene produces one short and one long transcript. When the long-form BdnfN transcript is not there, the growth factor BDNF is only produced in the body of the neuron, but not in its dendrites. This results in the production of too many immature synapses, which undermines learning and memory in mice.
Dr. Xu also discovered that mice with the same Bdnf gene-fault became extremely obese. Subsequently, other scientists starting examining the Bdnf gene in human beings and also found a link between obesity and the mutated Bdnf gene.
However, this is the only study to explain clearly how BDNF regulates body weight. According to Xu’s findings, insulin and leptin trigger BDNF synthesis in neuronal dendrites which facilitates the movement of their chemical messages from neuron-to-neuron via synapses. The aim is to maintain the insulin and leptin chemical signals moving properly along the neuronal highway to the right locations in the brain, where hormones set off a program which reduces appetite.
“If there is a problem with the Bdnf gene, neurons can’t talk to each other, and the leptin and insulin signals are ineffective, and appetite is not modified.”
Knowing that BDNF controls the movement of insulin and leptin signals via brain neurons is fine. The big question is “Can this faulty transmission be fixed?”.
If an additional long-form Bdnf transcript could be produced, using adeno-associated virus-based gene therapy, appetite suppression after eating might be restored in people with the faulty gene. This kind of gene therapy is usually effective and safe – however, delivering it across the brain blood barrier is not easy.
“The better approach might be to find a drug that can stimulate Bdnf expression in the hypothalamus. We have opened the door to both new avenues in basic research and clinical therapies, which is very exciting.”
Written by Christian Nordvist