Maintenance of the Body
stomach, is a powerful appetite stimulant. In fact, ghrelin ap-
pears to be the “dinner bell” or trigger for initiating a meal. Its
level peaks just before mealtime, signaling the brain that it is
time to eat, and then the level troughs out aFer the meal.
Long-Term Regulation of Food Intake
A key component of the long-term controls of feeding behavior
is the hormone
(“thin”). Secreted exclusively by adipose
cells in response to an increase in body fat mass, leptin indicates
the body’s total energy stores in fat tissue. (Tus adipose tissue
acts as a “±at-o-Stat” that sends chemical messages to the brain
in the form of leptin.)
When levels of leptin rise in the blood, it binds to receptors
in ARC that speciﬁcally (1) suppress the release of neuropeptide
Y and (2) stimulate the expression of CAR². NPY is the most
potent appetite stimulant known. By blocking its release, leptin
prevents the release of the appetite-enhancing orexins from the
LHA. Tis decreases appetite and food intake, eventually pro-
moting weight loss.
When fat stores shrink, leptin blood levels drop, an event
that exerts opposite eﬀects on the two sets of ARC neurons.
Consequently, appetite and food intake increase, and (eventu-
ally) weight gain occurs.
Initially it seemed that leptin was the magic bullet that obesity
researchers were looking for, but their hopes were soon dashed.
Rising leptin levels do promote weight loss, but only to a certain
Nutrient Signals Related to Energy Stores
Blood levels of
glucose, amino acids, and fatty acids provide information to
the brain that may help adjust energy intake to energy output.
±or example, nutrient signals that indicate fullness or satiety
Rising blood glucose levels.
When we eat, rising blood glu-
cose levels ultimately depress eating (±igure 24.23). During
fasting and hypoglycemia, this signal is absent, resulting in
hunger and “turning on” food-seeking behavior.
Te brain shows other responses to glucose and high-
caloric food as well. When we ingest sugar, the brain’s reward
(pleasure) system “gives oﬀ ﬁreworks” in the form of rising
dopamine levels to a greater or lesser degree. Perhaps this re-
sponse is the genesis of overeating (hedonistic) behavior.
Elevated blood levels of amino acids
depress eating, but the
precise mechanism is unknown.
Blood concentrations of fatty acids
provide a mechanism for
controlling hunger. Te larger the amount of fatty acids in
the blood, the more eating behavior is inhibited.
Gut hormones, including insulin and cholecysto-
kinin (CCK) released during food absorption, act as satiety
signals to depress hunger. Cholecystokinin, which blocks the
appetite-inducing eﬀect of NPY, is most important.
In contrast, glucagon and epinephrine levels rise during
fasting and stimulate hunger. Ghrelin (Ghr), produced by the
of GI tract)
Model for hypothalamic
command of appetite and food intake.
The arcuate nucleus (ARC) of the brain
contains two sets of neurons with opposing
effects. Activating the NPY and orexin
neurons enhances appetite, whereas
activating POMC/CART neurons has the
opposite effect. These centers connect with
interneurons in other brain centers, and
signals are transmitted through the brain
stem to the body. Many appetite-regulating
hormones act through the ARC, though they
may also exert direct effects on other brain
arcuate nucleus, CART
and amphetamine-regulated transcript,
releasing hormone, LHA
hypothalamic area, NPY