secretions, and the CNS in regulating appetite and feeding behaviors (Power and
Schulkin 2009 ). Yet, few have been shown to be biomarkers with high reliability in
predicting aspects of appetite and feeding behaviors in humans (de Graaf et al.
2004 ). The biomarkers most well studied are CCK and glucagon-like peptide
(GLP-1) associated with satiation and shortened meal duration and glucose, insulin,
leptin, gastric inhibitory polypeptide (GIP), ghrelin, and pancreatic polypeptide
(PP) peptide YY, also known as peptide tyrosine tyrosine (PYY), associated with
satiety (Gibbons et al. 2013 ).
Cholecystokinin (CCK) is secreted by the small intestine with receptors in the
vagus nerve, hindbrain, hypothalamus, and gut. CCK’s neurotransmitter functions
are associated with anxiety, sexual behavior, learning, and memory as well as
satiety. As noted above, CCK acting as a gut peptide is produced in response to
protein and fat ingestion and regulates gut motility, gastric emptying, pancreatic
enzyme secretion, and release of bile from the gallbladder (Moran and Kinzig
2004 ). CCK and leptin interact synergistically via the vagus nerve to innervate the
stomach and to shorten meal duration, that is, enhance satiation. However, it has
little effect on the frequency of meals or total daily food intake.
Glucagon-like peptide (GLP-1), YY, and PYY are produced in response to
carbohydrate and fat ingestion. GLP-1 stimulates the pancreas to produce insulin.
These signal molecules, along with others such as amylin, obestatin, and entero-
statin work through the CNS to suppress appetite and are often called‘satiety
signals’(Table10.4). GLP-1 can be used as a biomarker for satiation and in a
meta-analysis had a modest negative correlation with ratings of hunger (r=−0.26)
and a positive correlation with ratings of fullness or satiety (r= 0.38) (Verdich et al.
2001 ). Many other gut–brain peptides have satiation or satiety actions.
Ghrelin secreted by the stomach is the only gut peptide known to stimulate
feeding and is a reliable biomarker. It works in concert with the upregulating NPY
and agouti-related protein (AgRP), acting in the arcuate nucleus of the hypotha-
lamus. Sleep deprivation, increasingly prevalent in modern societies, is associated
with a rise in ghrelin, a decrease in leptin and increase in hunger, food consumption,
and obesity (Taheri et al. 2004 ). Ghrelin stimulates the release of growth hormone
and may be involved in reproductive endocrinology (Power and Schulkin 2009 ).
The pancreas, in addition to the synthesis and secretion of glucagon and insulin
for the regulation of glucose, produces PP. Depending on the mode of adminis-
tration and the site of action, in animal experiments PP both increases and decreases
appetite. Other pancreatic secretions are amylin which inhibits gastric emptying,
gastric acid and glucagon secretion, and enterostatin which is secreted in response
to fat digestion (Power and Schulkin 2009 ). Additional peptides secreted by the gut
and pancreas are listed in Table10.4which also includes the site of action in the
hypothalamus. The next section will briefly focus on the CNS mechanisms that are
involved in appetite and feeding behaviors.
Several peptides are involved in hypothalamic regulation of feeding and body
mass. These are grouped based on their behavioral effects into anabolic/orexigenic
peptides that promote feeding and increase of body mass or catabolic/anorexigenic
peptides involved in decreased food intake or termination of feeding. As indicated
218 L.S. Lieberman