"As a fat person I would be the first in line tomorrow if there was a magic cure, but the bottom line is, there is no magic cure," said Dr. Moe Lerner, a consultant with the Department of Health." So quoted a local newspaper and although the reporter took some liberties and distorted some of what I said, this statement reasonably reflects my personal dilemma. I have always maintained that I would be remiss as a physician if I did not acknowledge some of the medical and emotional sequelae of obesity. The aforementioned quote was solicited in response to a number of new scientific discoveries about obesity. The studies involve obesity genes, some metabolism enhancers that allegedly melt fat, and the reintroduction of diet pills that are surprisingly similar to their ancestors which were in vogue 30 years ago. One needs to understand the sophistication and complexity of the body's hormone system in order to be able to judge objectively the merits of these experimental treatments.

My hope is to introduce you to the fascinating world of hormones and metabolism by starting with the amazing "mother of all glands," the pituitary.

The Master Gland
When people speak of obesity resulting from a "glandular condition" they are usually referring to a process starting with a defect in the body's chief gland. The word pituitary is of Latin origin meaning secreting substance. This incredible combination computer and pharmacy is the size of a marble and sits dangling by a thin vascular stalk in a tiny chamber in the middle of the head. So many important functions are controlled by this puny organ that not all have been completely understood or discovered yet.

The Storehouse
The front half of the marble is truly a gland in that its cells manufacture hormones that circulate in the blood stream. The back half is a kind of storehouse for chemicals produced higher up in the brain.

The hormone oxytocin's job is to make the womb contract during childbirth. Antidiuretic (meaning to prevent urination) hormone is a close relative chemically to oxytocin and is also secreted by the back half, Its primary function, as the name indicates, is to stop us from urinating too much fluid. Without it we would become quickly dehydrated. In an effort to save vital bodily fluids it is not surprising that antidiuretic hormone also causes clamping down of blood vessels and is useful in situations of excessive bleeding or shock.

Hormones Flowing
The front of the gland has the greatest variety of chemicals. One of these, Adrenocorticotrophic Hormone, sends a message to tiny glands near the kidneys to produce steroids. These include some of the sex hormones that give males and females their different and often distinctive characteristics, especially at puberty. We typically think of steroids with reference to their abuse by some athletes. The male sex hormone progesterone and its many relative compounds are responsible for male characteristics and indeed the building up of muscle mass. But athletes who abuse this property eventually pay a dear price in that male sex hormones in excess also increase risks of heart attack, stroke, and aggressive, often antisocial, behavior. There are different kinds of steroids, many of which are responsible for helping our body avoid the ravages of inflammation and infection.
Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) sound like their involved in female reproduction but actually work on the sex organs in both men and women. FSH in women makes the egg sack get ready to release eggs, and in men increases sperm creation. LH stimulates release of the egg and prepares the body for pregnancy, while in males stimulates testosterone production which promotes masculine beard growth and other characteristics. The ancillary hormone prolectin (from the Latin meaning literally "before milk") promotes breast milk production. Melanocyte Stimulating Hormone stimulates the production of pigment in the skin, which darkens to protect against harmful light radiation.

Growth Hormone, also secreted from the back of the master gland, does exactly what its name implies by stimulating all parts of the body including muscles and bones. Too much of this substance can cause gigantism as seen in classic characters like Lurch (of the Addams Family series) and the late Andre The Giant of wrestling fame. Too little is responsible for many kinds of Dwarfism.

Metabolism
Thyroid Stimulating Hormone makes the thyroid gland increase the body's metabolism. The body needs a mechanism to get the heart racing and the energy furnace burning in order to respond to the stresses of living with action. Thyroid hormone also unlocks doors allowing other hormones to do their "thing". This is especially true of Anabolic Steroids and Growth Hormone. More salient is the fact that thyroid hormone eats up fat, cholesterol and sugar as a means of stoking the furnace. Realizing the potential of these properties, many experiments were conducted in which thyroid hormone was given to obese subjects and some weight loss did occur. The weight loss, however, eventually resulted at the expense of protein (muscles etc.) and there were many side effects. Recently, scientists discovered a gene which affects the receptors (Beta-Three Adrenergic) that control some forms of metabolic rate. It is postulated that some people born with defective receptors have a slower metabolism leading to obesity and diabetes. Among the problems negating this theory is the fact that this defect has also been found in thin people and there are many obese people who don't have the syndrome. Undaunted, pharmaceutical companies are testing a variety of drugs which they hope will speed up metabolic rates to circumvent the gene defect.

Hormone Replacement
In fairness, pituitary gland or related hormone deficiencies do exist and should be treated. These can be caused by a variety of situations from turnouts and trauma (eg. severing the small pituitary at its stalk, or sudden severe blood loss as occur rarely in difficult childbirth). It used to be next to impossible to gather enough of these hormones for distribution to those in need. Hundreds of the tiny glands were once collected at autopsies just to process enough growth hormone to supply one child with a Dwarfism disorder. But scientists now regularly breed genetically altered bacteria engineered to produce mass quantities of some of these hormones in the laboratory.

Of Mice and Men
My eyebrows were understandably raised somewhat with the recent discovery of a hormone named leptin (from the Greek meaning thin) in both experimental mice and humans. Leptin apparently signals the brain to make an individual feel satiated faster, stop eating and perhaps even speed up energy expenditure (fat burning). Interestingly, many fat mice have a defect in the gene that is responsible for this substance and scientists believe this is one of the reasons they are obese and often have diabetes. Accordingly, they have dubbed this abnormality the "ob gene".
The preliminary findings of experimentation with leptin are dramatic. When fat mice with the defect were given leptin (mass produced by genetic engineering of bacteria) the majority lost up to 30% of their weight in just two weeks. Virtually all of the weight loss was from fat and there were surprisingly few side effects.

The Catch
Scientists look forward to trials in humans, but the situation is far from clear. First of all, researchers have reason to conclude that not all large people have the gene defect. Furthermore, they also discovered a group of mice with extraordinarily high levels of leptin in their bodies but they were born with yet another defective gene, rendering leptin useless. In fact, these mice were not only obese and resistant to leptin, but they were almost all diabetics. The defective gene (and the mouse species) was thus dubbed "db" (for diabetes) as opposed to the earlier mentioned "ob" mice.
So for those who are fat and choose to lose weight, genetics may open new doors. Still I cannot avoid the feeling that the hormonal influences, both emotional and physical, the sense of hunger, and the incredibly complex fat reserve mechanisms that have taken millions of years to evolve in us, are complex to decipher. It may be years before all the clinical trials are completed and we have better answers. ß

---

Heretic Physician