C h a p t e r 1 0
Disorders of Nutritional Status
231
factor, and the percentage of dietary fat independent of
total caloric intake may play a part in the development
of obesity. Psychological factors include using food as a
reward, comfort, or means of getting attention. Eating
may be a way to cope with tension, anxiety, and mental
fatigue.
AdiposeTissue
Adipose tissue is no longer simply viewed as a reser-
voir for energy storage. Adipose tissue is now known
to express and secrete a variety of bioactive peptides,
known as
adipocytokines
(e.g., leptin, tumor necrosis
factor-
α
[TNF-
α
], interleukin-6 [IL-6]) that have auto-
crine, paracrine, and endocrine effects on the brain,
liver, skeletal muscle, and other tissues of the body.
24
In addition, adipose tissue expresses numerous recep-
tors that allow it to respond to afferent signals from
traditional hormone systems as well as the central ner-
vous system. Through this interactive network adipose
tissue is integrally involved in coordinating a variety
of physiologic processes including energy metabolism,
neuroendocrine function, and immune function. It is the
dysfunctional aspects of these processes that are impli-
cated in the pathogenesis and adverse effects of adipose
tissue excess or obesity.
AdiposeTissue as an Endocrine Organ
Adipose tissue is now recognized as an endocrine organ
that produces several hormones, including
leptin
, an
important mediator of body weight, and
adiponec-
tin
, which regulates sensitivity to insulin and may be
involved in the pathogenesis of type 2 diabetes.
24,25
Leptin (from the Greek meaning “thin”), a peptide
released from adipocytes, has led to renewed interest
in the function of adipose tissue and its role in energy
homeostasis. Leptin acts through binding to and activa-
tion of specific leptin receptors found in several periph-
eral tissues and in many areas of the brain, including
specific regions of the hypothalamus. Receptors in
these hypothalamic regions are known to be involved
in appetite, food intake, sympathetic nervous system
activity, temperature regulation, and insulin release by
the pancreatic beta cells. Leptin levels rise following
food intake, signaling the sensation of satiety, and fall
during fasting, stimulating the sensation of appetite.
Congenital leptin deficiency has been associated with
hyperphagia (excessive eating) and obesity, impaired
thermogenesis, insulin resistance, and hyperlipidemia,
all reversed by leptin treatment.
25
The biology of leptin
in normal individuals and its involvement in obesity
and obesity-related diseases is uncertain.
Adipose tissue also secretes
adiponectin
, which regu-
lates sensitivity to insulin and may be involved in the
pathogenesis of type 2 diabetes.
24,25
Whereas dysfunc-
tional adipose tissue increases the levels of certain other
hormones and adipocytokines, the levels of adiponectin
are decreased, leading to decreased insulin sensitivity,
proatherosclerosis, and a proinflammatory milieu that
can predispose the individual to
metabolic syndrome
(see Chapter 33) and its associated complications (includ-
ing type 2 diabetes and cardiovascular disease).
15,16
AdiposeTissue and the Inflammatory Process
Recent evidence suggests that excess adipose tissue is
also associated with a chronic inflammatory response,
which is characterized by abnormal cytokine produc-
tion; increased synthesis of acute-phase reactants, such
as C-reactive protein; and activation of proinflammatory
signaling pathways.
26
Systemic chronic inflammation has
been proposed to have an important role in the pathogen-
esis of obesity-related insulin resistance and development
of type 2 diabetes. It might also contribute to a state of
endothelial dysfunction, an abnormal lipid profile, hyper-
tension, and vascular inflammation, all of which promote
the development of atherosclerotic cardiovascular dis-
ease.
26,27
Although there is evidence that the proinflamma-
tory pathways are activated in adipose tissue in obesity,
the source of the inflammatory mediators remains unclear.
Besides adipocytes, adipose tissue contains a connective
tissue matrix and macrophages, which may contribute to
the production of inflammatory mediators.
Types of Obesity
Two types of obesity based on distribution of fat have
been described: upper body and lower body obe-
sity.
Upper body obesity
is also referred to as
central
,
abdominal
, or
visceral
obesity. Lower body obesity is
also known as
peripheral
or
gluteal-femoral
obesity.
Persons with upper body obesity are often referred to
as being shaped like an “apple,” compared with those
with lower body obesity, who are more “pear” shaped
(Fig. 10-3). The obesity type is determined by dividing
the waist by the hip circumference. A waist-to-hip ratio
greater than 1.0 in men and 0.8 in women indicates
upper body obesity. Research suggests that fat distribu-
tion may be a more important factor for morbidity and
mortality than overweight or obesity.
A
B
FIGURE 10-3.
Distribution of adipose tissue in
(A)
upper body
or central (visceral) obesity and
(B)
lower body or peripheral
(subcutaneous) obesity. People with upper body obesity are
often described as having an “apple-shaped” body and those
with lower body obesity as having a “pear-shaped” body.
