Regulation of Organic Metabolism and Energy Balance
term fasting, there is a marked decrease in the secretion of
the sex steroids and thyroid hormones, and an increase in the
secretion of adrenal glucocorticoids. These adaptations make
sense when we cons
ider that reproduction is energetically
costly, that thyroid hormones increase energy usage, and that
adrenal steroids stimulate production of substrates for gluco-
neogenesis that reach the liver via the circulation. In experi-
mental animals, these effects are almost completely eliminated
by administering leptin. This suggests that leptin normally
exerts a modulatory effect on the pathways that control the
secretion of these hormones (the possible role of leptin in
puberty is described in Chapter 17).
It should be emphasized that leptin is important for
matching of caloric intake to energy expenditure.
In addition, it is thought that various other signals act on
the hypothalamus (and other brain areas) over short peri-
ods of time to regulate individual meal length and frequency
(factors that reduce
appetite) cause the person to cease feeling hungry and set the
time period before hunger returns. For example, the rate of
insulin-dependent glucose utilization by certain areas of the
hypothalamus increases during eating, and this probably con-
stitutes a satiety signal. Insulin, which increases during food
absorption, also acts as a direct satiety signal. The increase in
metabolic rate induced by eating tends to raise body tempera-
ture slightly, which acts as yet another satiety signal. Finally,
some satiety signals are initiated by the presence of food
within the gastrointestinal tract. These include neural signals
triggered by stimulation of both stretch receptors and chemo-
receptors in the stomach and duodenum, as well as by several
of the hormones (cholecystokinin, for example) released from
the stomach and duodenum during eating.
Food intake is also strongly inﬂ uenced by the reinforce-
ment, both positive and negative, of such things as smell,
taste, and texture. In addition, the behavioral concepts of
reinforcement, drive, and motivation, described in Chapter 8,
must be incorporated into any comprehensive model of food-
cant factor that may alter food intake is
stress. However, it is difﬁ cult to make generalizations about
the effects of stress on food intake in humans. Some people
respond to stress by refraining from eating, whereas others
Although we have focused on leptin and other factors as
satiety signals, it is important to realize that a primary func-
tion of leptin is to increase metabolic rate. If a person is sub-
jected to starvation, his or her adipocytes begin to shrink,
as catabolic hormones mobilize triglycerides from fat cells.
This decrease in size causes a proportional reduction in leptin
secretion from the shrinking cells. The decrease in leptin con-
centration removes the signal that normally inhibits appetite
and speeds up metabolism. The result is that a loss of fat mass
leads to a decrease in leptin, and thus a decrease in BMR and
an increase in appetite. This may be the true evolutionary
signiﬁ cance of leptin, namely that its disappearance from the
blood results in a decreased BMR, thus prolonging life during
periods of starvation.
In addition to leptin, another recently discovered hor-
mone appears to be an important regulator of appetite.
(pronounced GREH-lin) is a 28-amino-acid peptide synthe-
sized and released primarily from endocrine cells in the fundus
of the stomach. Ghrelin is also produced in smaller amounts
from other gastrointestinal and non-gastrointestinal tissues.
Ghrelin has several major functions. One is to increase
growth hormone release from the pituitary—this is the deriva-
tion of the word
The major function of ghrelin perti-
nent to this chapter is to increase hunger by stimulating NPY
and other neuropeptides in the feeding centers in the arcuate
nuclei of the hypothalamus. Ghrelin also decreases the break-
down of fat and increases gastric motility and acid production. It
makes sense, then, that the major stimuli to ghrelin are fasting
(ghrelin levels increase just before a meal) and a low-calorie diet.
Ghrelin, therefore, participates in several feedback loops.
Fasting or a low-calorie diet leads to an increase in ghrelin.
This stimulates hunger and, if food is available, food intake.
The food intake subsequently reduces ghrelin, possibly
through stomach distention, caloric absorption, or some other
mechanism. The increase in ghrelin before a meal increases
gastric motility and acid secretion, preparing the stomach for
the impending meal.
Altered activity of integrating centers
Plasma leptin concentration
Energy intake > Energy expenditure
Postulated role of leptin in the control of total-body energy stores.
Note that the direction of the arrows within the boxes would be
reversed if energy (food) intake were less than energy expenditure.
Under what circumstances might the appetite-suppressing action
of leptin be counterproductive?
Answer can be found at end of chapter.