First of all, obesity is not created equal. From the Leptin view point, there is obesity with increased and with decreased Leptin levels. The ones with increased Leptin level are associated with very low sensitivity to Leptin and they represent the majority of all cases. However, in 10 to 15% of all obesity, Leptin levels are below normal, for example, it is true for Pima Indians. So, no matter what the reason — low level or low sensitivity — when Leptin does not work properly, obesity occurs.

Weight loss, no matter what the reason, results in decrease of Leptin level : when obese individuals were reduced by 15% of their initial body weight, the serum Leptin level decreased by 50%.

This can be the reason why dramatic weight gain is inevitable after food restriction is over. That’s why many diets fail. It is interesting, by the way, that in anorectics Leptin level quickly increases during re-feeding, much faster than body weight recovery. Some think this might be the reason why successful rehabilitation is so difficult in anorectics: their bodies perceive higher Leptin levels as higher fat content and resist furtherfeeding.

Genetically caused Leptin insufficiency in humans is rare and leads to severe obesity. In the human gnome, the locus for Leptin is situated close to locus for red hairiness, and indeed, two obese red-haired subjects with mutation around the Leptin locus in the gene, have been described. Only this and a very few other cases of the identification of Leptin gene mutation in humans have been described so far.

Does this mean that Leptin therapy is only for those few or can it include the 5-10% of obesity with low circulating Leptin levels? It is not clear. There is hope that for those with a high level but low sensitivity to Leptin (this represents the majority), higher doses of exogenous — injected or infused — Leptin should do.

In 2008, the Nature journal reported about unpublished results of ongoing clinical trials. Under-skin injections of 0.3 mg of Leptin for every kg of body weight for 6 months resulted in 8 subjects’ weight loss that totaled an average of 7.1 kg (1.7 kg in placebo group). Sounds promising?

Not so fast. “Leptin may not be a miracle pill,” says Dr. JoAnn Manson, Harvard Medical School. Actually it is no pill at all (maybe not yet). One of the problems with Leptin is in the delivery method. Given once a day as an injection into the abdomen (intraperitoneal) it is generally ineffective. Subcutaneous permanent infusion as we had the chance to see, is more effective but much less feasible as you can imagine.

The most effective way is injecting Leptin directly into the fluid that circulates inside the brain and spinal cord (intracerebroventricular injection) though one will probably have to have a really good reason to commit to this kind of therapy since it means permanently having a tube injected between the vertebrae and penetrating nervous tissue to reach the internal duct.

Another problem is that over time, adults seem to lose their responsiveness to Leptin.

On the other hand, researchers are in the process of filing for a patent on the new, long-lived form of Leptin.

There is hope in the prospect of gene therapy that is just starting to be investigated in animals. This hopefully will repair mistakes in Leptin production. As to the reduced sensitivity, it is not completely clear yet how this problem can be approached, but Stanford medical school has recently reported that the newly identified protein may overcome Leptin resistance

However, all these theories are in the beginning stages. Who will be eligible? Is weight loss the goal or just the corresponding diseases (co-morbidities) are? One thing is clear. Do not expect your doctor to prescribe you a course of injections soon. Leave the bottle of supplemens called Leptin on the shelves. On the other hand, Leptin is so fashionable that I would not be surprised if supplement manufacturers fail to grasp the opportunity to exploit these circumstances. When you see anything claiming Leptin-like effects — do not believe your eyes! Not quite yet!