672 Chapter 19
CLINICAL APPLICATION
Metabolic syndrome refers to a constellation of symptoms
often associated with obesity. Obesity, especially involving
visceral fat, promotes insulin resistance, impaired glucose
tolerance, and type 2 diabetes (as will be discussed). These
are often associated with hypertension and dyslipidemia,
a term that refers to the “atherogenic lipid triad”: elevated
blood triglycerides, low levels of HDL cholesterol (chapter 13,
section 13.7), and high levels of small, dense LDL particles.
By promoting atherosclerosis, these conditions increase the
risk of cardiovascular disease. There is also a greater prev-
alence of chronic kidney disease. A person has metabolic
syndrome when there is central obesity (defined by a waist
circumference greater than certain values) combined with
two of the other conditions described above. Metabolic syn-
drome raises the risk of heart disease and stroke by a factor
of three, and the incidence of metabolic syndrome has been
increasing with the rising prevalence of obesity and type 2
diabetes mellitus, described in section 19.4.obesity. According to the standards set by the National Insti-
tutes of Health, a healthy weight is indicated by a BMI between
19 and 25. A BMI in the range of 25.0 to 29.9 is described as
“overweight;” a BMI of over 30 is “obese.” According to a
recent study, however, the lowest death rates from all causes
occurred in men with a BMI in the range of 22.5 to 24.9, and in
women with a BMI in the range of 22.0 to 23.4. Recent surveys
indicate that over 60% of adults in the United States are either
overweight (with a BMI greater than 25) or obese (with a BMI
greater than 30).
Obesity is strongly associated with type 2 diabetes mellitus,
discussed later in this chapter. Childhood obesity and associated
childhood type 2 diabetes mellitus have increased dramatically
in recent years. For example, one study demonstrated a 36%
increase in childhood obesity between 1988 and 1994; another
showed a tenfold increase in the incidence of childhood type 2
diabetes mellitus between 1982 and 1994. According to a study
done by the Rand Corporation, obesity is a greater risk factor in
chronic diseases than either smoking or drinking!
Clinical Investigation CLUES
Marty had a BMI of 34, and the physician stated that he
has to lose weight because he is in danger of developing
diabetes and cardiovascular diseases.- What is the significance of Marty’s BMI
measurement? - What condition does the physician believe Marty
might have? - What other blood measurements might be made to
confirm that belief?
Regulation of Hunger
and Metabolic Rate
Ideally, we should eat the kinds and amounts of foods that
provide adequate vitamins, minerals, essential amino acids,
and calories. Proper caloric intake maintains energy reserves
(primarily fat and glycogen) and maintains body weight that is
optimum for health.
Hunger and eating behavior are at least partially controlled
by areas of the hypothalamus. Lesions (destruction) in the ven-
tromedial area of the hypothalamus produce hyperphagia, or
overeating, and obesity in experimental animals. Lesions of
the lateral hypothalamus, by contrast, produce hypophagia and
weight loss.
The neurotransmitters in the brain that may be involved in
the control of eating are under investigation, and many have been
implicated. Among those are the endorphins (naloxone, which
blocks opioid receptors, suppresses overeating in rats); norepi-
nephrine (injections into the brains of rats cause overeating); and
serotonin (intracranial injections suppress overeating in rats).
These findings have been applied to humans in the design of
weight-loss drugs. However, previous drugs that reduced hunger
by elevating brain levels of serotonin were withdrawn from the
market due to serious side effects. The FDA has more recently
approved two new medications. One selectively stimulates the
serotonin receptors; the other contains a sympathomimetic drug,
which stimulates adrenergic receptors to reduce appetite.Arcuate Nucleus of the Hypothalamus
Neurotransmitters from different brain regions, and hormonal
regulators carried by the blood, are believed to regulate hunger by
influencing a particular center in the hypothalamus known as the
arcuate nucleus. Neurons from the arcuate nucleus, in turn, proj-
ect to other brain areas. One of these is the paraventricular nucleus
of the hypothalamus, an area associated with hunger (destruction
of this nucleus causes overeating). Neurons in the arcuate nucleus
also send axons to the lateral hypothalamus, an area known as a
“feeding center;” axons from here project to the nucleus accum-
bens of the forebrain (chapter 8; see fig. 8.21), which is believed
to be involved in the rewarding aspects of eating.
In terms of hunger regulation, the arcuate nucleus contains
two groups of neurons. One group of neurons, the anorexigenic
neurons, suppresses hunger. This group contains POMC (pro-
opiomelanocortin) neurons, which secrete a large polypeptide
that is converted into a melanocortin family of molecules,
including MSH (melanocyte-stimulating hormone). MSH
acts to decrease appetite by binding to its melanocortin recep-
tors in the hypothalamus.
Another group of neurons in the arcuate nucleus, the
orexigenic neurons, promotes hunger. These neurons release
two hunger-promoting neurotransmitters: neuropeptide Y
and AgRP ( agouti-related protein ). Neuropeptide Y stimulates
hunger directly; AgRP antagonizes MSH at the melanocortin
receptor, thereby inhibiting the appetite-suppressing action
of MSH. When eating results in an abundance of circulating