Obesity

Obesity

Adipose tissue has three primary functions. Two are well
recognized and defined: to serve as the site for storage of
energy-rich fatty acids in the form of triglyceride and to effect
the controll ed release of the constituent fatty acids and glycerol
in response to neural , endocrine, and local signals for
metabolism at di stant sites. A third and increasingly important
role of adipose tissue is its function as an endocrine organ,
releasing a variety of factors that regulate metabolism. Obesity
is defined as astate of excessive adipose tissue mass and is
best viewed as a syndrome or group of diseases rather than as
a single di sease entity. The importance of thi s state derives
from its high prevalence in our society and i ts associati on with
serious morbidi ty, not the least of which i s a marked increase in
the prevalence of type 2 diabetes. Specific syndromes of
obesity, both in animal models and in humans, are associated
with identified neural , endocrine, or genetic causes. However,
the pathogenesis of obesity i n the vast majority of humans is
unknown and remains an unexplained chronic excess in calori c
intake relative to energy needs. An understanding of obesity
and its consequences requires the investigati on of the many
factors that control energy intake and energy expenditure, the
two interrel ated components of the energy -bal ance equation. As
with our understanding of pathogenesis, our understanding of
the molecular connection between obesity and its most
important complications is limited, and our approach to therapy,
as defined by clinical success rate, is extremely poor. In this
chapter, we will review the current understanding of the
pathogenesis, complications, and treatment of obesity.

DEFINITION AND INDICES OF OBESITY

The distribution of body weight in the population is a continuous
function without a clear separation between lean and obese.
The most medically relevant criterion relates to the
identificati on of a weight that confers morbidity. The selection
of a specific threshold is somewhat arbitrary, and a number of
different criteri a have been used. Initially, the approach was
through the use of life insurance data (Metropolitan Life) that
assess mortality as a function of body weight per height,
adjusted for frame size, with obesity defined on purely
statistical grounds as a weight that i s 20% or more above the
average weight per height. Over the past decade,
calculation of body mass index (BMI) has evolved as a more
standard measurement used to correlate weight with morbidity
and mortality. BMI i s calculated by determining weight in
kilograms and dividing by the height in meters squared. This
measurement has been used to define four classes of body
weight. A BMI of less than 18.5 is considered underweight and
carries a modestly increased risk of morbidity and mortality. A
BMI between 18.5 and 24.9 is considered normal . A BMI of more
than 25.0 but less than 29.9 i s considered overweight or
preobese and, statistically, carries a slightly increased risk of
comorbidi ties such as diabetes and cardiovascular disease
compared with the risk in normal -weight individuals. A BMI of
more than 30 is considered in the category, which is further
subdivi dedinto class I (BMI, 30 to 39.9), class II (BMI, 40 to
49.9), and class III (BMI, >50). These categories of obesity
carry respective risks of comorbidities that are moderate,
severe, and very severe, respectively . A second approach to
defining the obese state involves quantitation of adipose tissue,
either directly or indirectly. Values are obtained for a reference
group viewed as normal , and obesity is defined as level's of
adiposity exceeding that seen in the reference group.
The definition of obesity can be refined on the basis of the
realizati on that the accumulation of adipose tissue in different
depots has distinct consequences. Thus, many of the most
important complications of obesity, including insulin resistance,
diabetes, hypertension, and hyperlipidemia, are linked to the
amount of intra abdominal fat, rather than to lower-body fat
(i .e., buttocks and leg) or subcutaneous abdominal fat.
Abdominal fat, typically evident on physical examination, can be
estimated by determining the waist -to-hip circumference ratio
(with a ratio >0.72 considered abnormal), or more accurately
quantified by dual -energy x-ray absorptiometry (DEXA)
scanning or computed tomography.

PREVALENCE OF OBESITY
It i s obvious from casual inspection of the populati on that
obesity is prevalent in the United States, although the precise
prevalence figures vary to some degree, depending on the
nature of the population surveyed. In the United States, the
prevalence of overweight or preobesity , i .e., a BMI of 25 to
29.9, has remained fairly constant at 40% for men and 24% for
women over roughly a 30-year period (1960 to 1994). However,
in the same period, the prevalence of a BMI higher than 30 has
risen significantly, especially over the past decade. In 2001
more than 20% of all adults had a BMI greater than 30,
compared with 12% of all adults in 1991. Obesity among adults
aged 18 to 29 doubled from 7% i n 1991 to 14% in 2001. Among
people aged 50 to 59, more than 25% have a BMI greater than
30. When analyzed by race and ethnicity, a BMI
greater than 30 was most prevalent among black, non -Hispanic
people. Interestingly, rates of obesity correlate inversely with
educational level and areal most twice as high in adul ts who
have not completed high school as in adults who have finished
college or graduate school. This indicates that
environmental and cultural factors can act as inhibitors to
weight gain. At present 60% of the male population and 50% of
the female population have a BMI greater than 25, which is
associated with increased risk of morbidity and mortality.
As noted above, an important predictor of the morbidity and
mortality associated with obesity is the quantity of visceral fat.
A rough index of the relative amounts of visceral and abdominal
fat is the waist-to-hip ratio. The alternative patterns of body -fat
distributi on have been described as pear shaped (low waist -to-
hip ratio) and apple shaped (higher waist -to-hip ratio). When
the waist-to-hip ratio i s less than 0.8, the relative risk of
morbidities associated with obesity is l ower than when the
waist-to-hip ratio is greater than 1.0. Hence, the metabolic
syndrome, which i s a clustering of obesity and other
cardiovascular risk factors, is more likely to be associated with
visceral obesity.

Next to Obesity Part II