"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 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.
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.
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.
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.
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
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