chapter 5
Thermodynamics, Chemical Kinetics, and Energy Metabolism
from the third group; and from the fourth group by
selection of whole-grain products (See also
Chapter 9).
5.6 Obesity
The first law of thermodynamics states that the amount of
stored energy equals the difference between energy intake
and energy expenditure. The principal storage of energy
is that of triglycerides in adipose tissue. Energy stores are
essential for survival during times of energy deprivation
(Chapters 18 and 22).
Energy stores in an adult are maintained at a relatively
constant level throughout life. However, even a small im-
balance in energy intake over long periods of time will
have a significant effect on energy storage. For example,
suppose a non obese adult’s energy intake exceeds expen-
diture by about 1
% daily for one year. This amounts to
an excess of 9,000 kcal and corresponds to a weight gain
of about 2.5 lb (1.15 kg) per year. 3,500 kcal of chemi-
cal energy is equivalent to 1 lb (0.45 kg) of adipose tissue.
Weight gain in most people is attributable to overconsump-
tion of palatable, energy-dense foods (e.g., lipids) and a
sedentary lifestyle. Childhood obesity is a risk factor for
obesity in adulthood.
Obesity is a consequence of a positive energy bal-
ance, i.e., input is greater than output. Body mass index
(BMI) is the most useful parameter in assessing the mag-
nitude of obesity (Table 5-6). A BMI of 19-25 is consid-
ered healthy, 26-29.9 is moderately overweight, and 30
or greater is obese. Obesity is the most common health
problem in the developed world, and it is estimated that
obesity affects about one third of the U.S. adult popula-
tion. In developed nations, the prevalence of obesity is
higher among economically deprived people, whereas in
developing nations, the relatively affluent have a higher
A BMI greater than 28 is an independent risk factor
(3^4 times higher than the general population) for cardio-
vascular diseases (Chapter 20), diabetes mellitus type
2 (Chapter 22), and stroke. The prevalence of obesity-
associated morbidity depends on the location of fat distri-
bution in the body. Intra-abdominal or visceral fat deposits
are associated with higher health risks than gluteofemoral
adipose tissue fat accumulation.
In experimental animals and possibly in humans, en-
ergy intake influences the aging process as well as the
onset of aging-associated diseases. Energy restriction in
animals, without altering their optimal nutritional status,
increases the average life span but not the maximal life
span. This beneficial biological response to energy re-
striction has been attributed to the attenuation of oxida-
tive damage to proteins, lipids, and DNA (Chapter 14).
During aging, despite increased body fat, there is a lin-
ear decrease in food intake and metabolism over the life
Biochemical M ediators of Obesity
The regulation of energy intake and expenditure is
achieved by coordinating the effects of endocrine media-
tors and neural signals that arise from adipose tissue, en-
docrine glands, neurological and gastrointestinal systems.
All of the information finally is integrated by the central
nervous system (Figure 5-6).
One of the most significant mediators of the energy
store in the adipose tissue is
(from the Greek
meaning “thin”). Leptin is a protein of 167 amino acid
residues that is synthesized in adipocytes. Its synthesis is
increased by insulin, glucocorticoids, and estrogens and
is decreased by ^-adrenergic agonists. The role of leptin
in obesity comes from studies on rodents. In genetically
obese mice (Ob/Ob), the observed gross obesity is due to
absence of leptin production in the adipocytes. Leptin’s
action on energy metabolism is mediated by receptors in
many cells and it binds specifically to a receptor in the
The action of leptin involves at least two pathways. Dur-
ing starvation and weight loss, adipose tissue is decreased
with consequent low levels of leptin. The low level of lep-
tin leads to production of neuropeptide Y, which is syn-
thesized in the arcuate nucleus of the hypothalamus and is
transported axonally to the paraventricular nucleus. Neu-
ropeptide Y binds to its receptor and functions as a potent
appetite stimulant. The overall effect is increased appetite,
decreased energy expenditure and temperature, decreased
reproductive function (infertility), and increased parasym-
pathetic activity. An opposite set of events occurs when
the leptin levels rise, except that the effects are mediated
by melanocyte-stimulating hormone (MSH) that binds to
the melanocortin 4 receptor (MC4-R). The MSH binding
to MC4-R initiates several biological responses, includ-
ing decreased appetite, increased energy expenditure, and
increased sympathetic activity (Figure 5-7).
In humans, obesity is a complex disease because of the
redundancy of systems that regulate energy storage. There
are inherited disorders of hyperphagia leading to obesity
with associated clinical features such as hypogonadism
and mental retardation. One hereditary disorder is
Willi syndrome
(Chapter 26), which is the most prevalent
form of dysmorphic genetic obesity
( 1
1 0
0 0 0
2 0 , 0 0 0
previous page 112 Bhagavan Medical Biochemistry 2001 read online next page 114 Bhagavan Medical Biochemistry 2001 read online Home Toggle text on/off