CENTRAL  SOUTH  DAKOTA MEDICAL NEWS
The Clinical View
by P.E. HOFFSTEN, M.D.

THE MIRACLE OF LEPTIN

     Our hormonal system is unbelievably complex.  An hormone is a chemical that is secreted in one part of the body, released into the blood stream and then acts as a messenger to other parts of the body.  A common example is insulin which is secreted in the pancreas and acts all over the body telling cells to take up sugar.  Many of our diseases represent hormone deficiencies.  Diabetes mellitus is an example of a disease that results from hormone deficiency of insulin.  Most people can name several different hormones such as insulin, cortisone, thyroid hormone, estrogen, and testosterone.  These hormones have been known for many years and the diseases that result from their deficiency have been well characterized.

       Modern chemical research techniques have now identified more than 100 different hormones.  Although their deficiency states have not all been well characterized.  One of the tragedies of a hormone deficiency is that it is not necessarily fatal or if it is fatal, the person experiences a prolonged “years” of discomfort, disability, and change in physical appearance before they die.  A disease called myxedema that results from the lack of thyroid hormone can be present for 20 or more years with a person lacking energy, gaining weight, deepening of their voice, coarsening their skin and slowing their thinking.  Diabetes does not result in an immediate fatality; instead the person experiences 10-40 years of insulin injection, blindness, kidney failure, loss of legs, struggles with an excessive weight problem.  Thus hormone deficiencies are a major cause for discomfort and disability.

       About 10 years ago, a hormone called Leptin was discovered.  It was initially discovered in mice that were noted to become massively overweight.  These mice ate excessively, and soon became so fat they couldn’t walk.  Some very smart researcher thought maybe it was due to a hormone excess or a hormone deficiency.  Eventually, the hormone “Leptin” was isolated.  The gene that made it was characterized and now this hormone can be made in a barrel by bacteria that have that gene planted into them.  We have learned that leptin is one of the pivotal hormones that suppresses your appetite and your body weight.  When the fat mice that lack this hormone were provided with daily  injections of it, the mouse’s body weight went back to normal and they weren’t fat mice anymore.  The application of this to humans and our overweight problem is awesome to contemplate.

       Soon after the mouse hormone was isolated and it’s gene sequenced, the same type of hormone was found in hormone was found in humans, a blood test was developed that could measure serum leptin levels and it was found that overweight individuals have more of this hormone in their blood than did people whose weights were “ normal”.  Thus there is another correlate of diabetes.  Most diabetic individuals have much more insulin than normal people but they are simply not as sensitive to it.  Overweight people have more leptin than normal but they are not sensitive to it.

       Now comes the miracle.  If the human being simply did not have enough leptin to control their weight at the normal level, what would be the predicted  consequence.  What would happen if a person had no leptin at all?

       Such a person was described in the New England Journal of Medicine several years ago. A very overweight young man had reached pubertal age but nothing happened.  The levels of fat in  his blood were very high and his insulin levels were also very high.  When his blood was checked for the presence of leptin, there was none there.  Zero.  Not low but none at all.

       Doctors  began to give him injections of leptin and in only 4 months time, he lost a massive amount of weight.  His high blood fat levels returned to normal, pubertal changes began to occur.  The leptin injection was subsequently stopped and all the problems that he had recurred. Leptin deficiency then provides a classical example of a hormonal deficiency that makes people’s lives miserable but doesn’t kill them quickly.

       Considering that one third of our population is overweight, what a miracle it would be if we could find a simple medication that would reverse excessive appetite and allow a person’s weight to come back towards a more normal level.  It was a high disappointment when researchers discovered that very overweight individuals had more leptin in their blood than do normal people.  Thus the idea that more leptin yet would help them was kind of shaky.  The real answer is to find how to adequately stimulate the leptin receptor on ourselves if our leptin isn’t doing  the job.

       Drug companies and biotechnical research organizations are working feverishly on this problem.  Slight modifications of the leptin molecule that will allow it to remain on its receptor longer or not be eliminated from the body so quickly are being investigated.  The day some drug company finds a safe, effective leptin like molecule, gets it by the FDA and onto the market is coming.  You better buy stock in that company in a hurry because that is going to be the most colossal hormone medication ever discovered.

       Research in the past 20 years has demonstrated that contrary to popular beliefs, overweight people are not simply slothful pigs who eat too much.  Instead it has been clearly recognized that poorly understood hormonal imbalances result in a person becoming overweight. Imbalances operate over many years time, eventually creating diabetes, hypertension, heart disease and wear and tear arthritis.  While these hormone imbalances can be overcome with heroic discipline that  doesn’t seem to work for the great group of people who are overweight. The stresses and strains of life are enough for normal weight people.  Overweight people have all of the same stresses and strains plus the travails of trying to control their weight through a disciplinary step that fatigues.  What a miracle it will be when a simple hormone replacement allows a person’s weight to come into a normal range and stay there with no disciplinary effort necessary.