Human Physiology, 14th edition (2016)

670 Chapter 19

Figure 19.2 A flowchart of energy pathways in the
body. The molecules indicated in the top and bottom are those
found within cells, while the molecules in the middle portion of
the figure are those that circulate in the blood.

Hydrolysis of dietary

or energy-reserve

sources (in cells)

Circulating energy

substrates

(in blood)

Intermediates

of aerobic

respiration

(in cells)

Pyruvic

acid

NH 2

Urea

Acetyl

coenzyme A

Citric

acid

cycle

CO 2 + H 2 O + ATP

Fatty acids,

glycerol,

ketone bodies

Glucose,

lactic

acids

Amino

acids

Triglycerides Polysaccharides Proteins

acids and glycerol during times of fasting. Because the synthesis

and breakdown of fat is controlled by hormones that act on the

adipocytes, the adipocytes traditionally have been viewed simply

as passive storage depots of fat. Recent evidence suggests quite the

opposite, however; adipocytes may themselves secrete hormones

that play a pivotal role in the regulation of hunger and metabolism.

Development of Adipose Tissue

Some adipocytes appear during embryonic development, but

their numbers increase greatly following birth. This increased

number is due to both mitotic division of the adipocytes and the

conversion of preadipocytes (derived from fibroblasts) into new

adipocytes. This differentiation (specialization) is promoted by

a high circulating level of fatty acids, particularly of saturated

fatty acids. This represents a nice example of a negative feedback

loop, where a rise in circulating fatty acids promotes processes

that ultimately help to convert the fatty acids into stored fat.

The differentiation of adipocytes requires the action of a

nuclear receptor protein—in the same family as the receptors for

thyroid hormone, vitamin A, and vitamin D—known as  PPAR (^) g.
( PPAR is an acronym for p eroxisome p roliferator a ctivated r ecep-
tor, and the g is the Greek letter gamma, indicating the subtype of
PPAR.) Just as the thyroid receptor is activated when it is bound
to its ligand, PPAR g is activated when it is bound to its own spe-
cific ligand, a type of prostaglandin. When this ligand binds to
the PPAR g receptor, it stimulates adipogenesis by promoting the
development of preadipocytes into mature adipocytes. The PPAR g
nuclear receptor protein is a transcription factor that acts as a
“master switch” in the formation of adipocytes. The number of
adipocytes increases during childhood, but in adulthood—despite
evidence of a slow turnover of adipocytes—the total number is
relatively stable.
However, even in adults, the activation of PPAR g stimu-
lates the formation of new adipocytes. This occurs predomi-
nately in the subcutaneous tissue, where small adipocytes are
produced, rather than in the large adipocytes characteristics of
deep visceral fat. This activation of PPAR g and the resulting
formation of new subcutaneous adipocytes increases the sen-
sitivity of the body to insulin, helping to lower blood glucose.
Endocrine Functions of Adipose Tissue
Adipose tissue secretes regulatory molecules, collectively termed
adipokines, which regulate hunger, metabolism, and insulin sen-
sitivity. These adipokines are secreted into the blood and act on
distant target organs, and so qualify as hormones.
In obesity, the enlarged adipocytes secrete an adipokine that
attracts monocytes that can turn into macrophages. As a result,
the macrophage content of the adipose tissue of an obese person
can be as high as 50%. Tumor necrosis factor-alpha  (TNF a ) is
secreted by the macrophages and can reduce the ability of skeletal
muscles to remove glucose from the blood in response to insu-
lin (that is, promote insulin resistance ). The secretion of TNF a ,
as well as the release of free fatty acids from the adipose tissue
(which also acts on skeletal muscles to promote insulin resis-
tance), is increased in obesity and type 2 diabetes mellitus.
chapter 5, and can be reviewed by referencing table 5.1. The
hormonal regulation of metabolism is described in several sec-
tions of this chapter.

Regulatory Functions

of Adipose Tissue

Many scientists believe that it is difficult for a person to lose (or
gain) weight because the body has negative feedback loops that
act to “defend” a particular body weight, or more accurately, the
amount of adipose tissue. This regulatory system has been called
an adipostat. When a person eats more than is needed to main-
tain the set point of adipose tissue, the person’s metabolic rate
increases and hunger decreases. Homeostasis of body weight
implies negative feedback loops. Hunger and metabolism (act-
ing through food and hormones) affect adipose cells, so in terms
of negative feedback it seems logical that adipose cells should
influence hunger and metabolism.
White adipose tissue (white fat) is the major site of energy
storage in the body. In white fat adipocytes (fat cells), triglycerides
are stored in a single, large droplet within each cell. The triglyc-
erides are formed during times of plenty and are hydrolyzed (in
a process termed lipolysis ) by lipase enzymes to release free fatty