Regulation of Organic Metabolism and Energy Balance
589
example, adipose tissue cells in the abdomen are much more
adept at breaking down fat stores and releasing the products
into the blood.
What is known about the underlying causes of obesity?
Identical twins who have been separated soon after birth and
raised in different households manifest strikingly similar body
weights and incidences of obesity as adults. Twin studies thus
indicate that genetic factors play an important role in obesity.
It has been postulated that natural selection favored the evo-
lution in our ancestors of so-called
“thrifty genes,”
which
boosted the ability to store fat from each feast in order to sus-
tain people through the next fast. Given today’s relative abun-
dance of high-fat foods in many countries, such an adaptation
is now a liability.
Despite the importance of genetic factors, psychologi-
cal, cultural, and social factors can also play a signifi cant role.
For example, the increasing incidence of obesity in the United
States and other industrialized nations during the past 30
years cannot be explained by changes in our genes.
Much recent research has focused on possible abnor-
malities in the leptin system as a cause of obesity. In one
strain of mice (shown in the chapter-opening photo), the
gene that codes for leptin is mutated so that adipose tis-
sue cells produce an abnormal, inactive leptin, resulting in
hereditary obesity. The same is
not
true, however, for the vast
majority of obese people. The leptin secreted by these people
is normally active, and leptin concentrations in the blood are
elevated, not reduced. This observation indicates that leptin
secretion is not at fault in these people. Thus, such people
may be leptin-resistant in much the same way that people
with type 2 diabetes are insulin-resistant. Moreover, there
are multiple genes that interact with one another and with
environmental factors to infl uence a person’s susceptibility to
weight gain.
The methods and goals of treating obesity are now
undergoing extensive rethinking. An increase in body fat must
be due to an excess of energy intake over energy expenditure,
and low-calorie diets have long been the mainstay of therapy.
However, it is now clear that such diets alone have limited
effectiveness in obese people; over 90 percent regain all or most
of the lost weight within fi
ve years. Another important reason
for the ineffectiveness of such diets is that, as described earlier,
the person’s metabolic rate decreases as leptin levels decrease,
sometimes falling low enough to prevent further weight loss
on as little as 1000 calories a day. Because of this, many obese
people continue to gain weight or remain in stable energy bal-
ance on a caloric intake equal to or less than the amount con-
sumed by people of normal weight. These persons must either
have less physical activity than normal or have lower basal met-
abolic rates. Finally, at least half of obese people—those who
are more than 20 percent overweight—who try to diet down
to desirable weights suffer medically, physically, and psycho-
logically. This is what would be expected if the body were “try-
ing” to maintain body weight (more specifi cally fat stores) at
the higher set point.
Such studies, taken together, indicate that crash diets
are not an effective long-term method for controlling weight.
Instead caloric intake should be set at a level that can be
maintained for the rest of one’s life. Such an intake in an
overweight person should lead to a slow, steady weight loss
of no more than one pound per week until the body weight
stabilizes at a new, lower level. Most important, any program
of weight loss should include increased physical activity. The
exercise itself uses calories, but more importantly, it partially
offsets the tendency, described earlier, for the metabolic rate
to decrease during long-term caloric restriction and weight
loss. Also, the combination of exercise and caloric restriction
may cause the person to lose more fat and less protein than
with caloric restriction alone, although a recent study sug-
gests this may not always be true. To restate the information
of the previous two sentences in terms of control systems,
exercise seems to lower the set point around which the body
regulates total-body fat stores.
Let us calculate how rapidly a person can expect to lose
weight on a reducing diet (assuming, for simplicity, no change
in energy expenditure). Suppose a person whose steady-state
metabolic rate per 24 h is 2000 kcal goes on a 1000 kcal/day
diet. How much of the person’s own body fat will be required
to supply this additional 1000 kcal/day? Because fat contains
9 kcal/g:
1000 kcal/day
=
111 g/day, or 777 g/week
9 kcal/g
Approximately another 77 g of water is lost from the
adipose tissue along with this fat (adipose tissue is 10 percent
water), so that the grand total for one week’s loss equals 854 g,
or 1.8 pounds. Thus, even on this severe diet, the person can
reasonably expect to lose approximately this amount of weight
per week, assuming no decrease in metabolic rate occurs.
Actually, the amount of weight lost during the fi rst week will
probably be considerably greater because a large amount of
water may be lost early in the diet, particularly when the diet
contains little carbohydrate. This early loss is not really elimi-
nation of excess fat but often underlies the extravagant claims
made for fad diets.
Eating Disorders: Anorexia
Nervosa and Bulimia Nervosa
Two of the major eating disorders are found primarily in
adolescent girls and young women. The typical person with
anorexia nervosa
becomes pathologically obsessed with her
weight and body image. She may decrease her food intake so
severely that she may die of starvation. It is not known whether
the cause of anorexia nervosa is primarily psychological or bio-
logical. There are many other abnormalities associated with
it—cessation of menstrual periods, low blood pressure, low
body temperature, and altered secretion of many hormones,
including increased levels of ghrelin. It is likely that these are
simply the results of starvation, although it is possible that
some represent signs, along with the eating disturbances, of
primary hypothalamic malfunction.
Bulimia nervosa,
usually simply called bulimia, is a dis-
ease characterized by recurrent episodes of binge eating. It is
usually associated with regular self-induced vomiting, use of lax-
atives or diuretics, as well as strict dieting, fasting, or vigorous
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