neuron

Various neurological factors play a role in the development of obesity.  We have a lot to learn, but from looking at the various physiological abnormalities and their observed clinical impact, we can get some idea of what is going on.

Appetite and food consumption is regulated at the neurological level, the hypothalamus being particularly important.  A variety of neuropeptides regulate hunger and appetite like NPY and PYY.

One of the most important pathways is the POMC/Agouti-related protein pathway.  There, POMC activation leads to a melanocortin pathway that regulates appetite, reducing it.  Agouti-related protein does the opposite, inducing hunger.

Stimulation of POMC such as that might be caused by Contrave, a new anti-obesity treatment, is often modulated by the release of beta endorphin, which induces tolerance.

Leptin, an emerging messenger for its role in obesity, has neurological activities.  It binds to the leptin receptor, stimulates POMC, then MSH and MC4 receptor.  Mutations in this pathway can cause obesity – mutations in MC4 specifically are responsible for 2-5% of obesity.  In those cases, the graph of one’s weight can shoot up to reach the graph of one’s height on a chart.

Additional neurologically linked abnormalities can induce weight gain.  Prader-Willi syndrome, which is characterized by damage to the hypothalamus, causes characteristic weight gain.  Damage to the hypothalamus tends to result in weight gain preferentially over weight loss as this preserves life while losing enough weight would certainly result in death.

Mutations in the HESX 1, LHX 3, Prop1, Pit1 pathway that leads to pituitary development can result in weight abnormalities.

These neurological activities are leading to active research in the development of treatments.  Qnexa causes 10% weight loss over a period of months and is composed of the anti-epileptic topiramate along with the amphetamine relative, phentermine.  There, topiramate has various effects on GABA and induces a great deal of weight loss.

These various neurological factors hint at potential areas of research to better understand the pathogenesis of obesity.