account, in part, for the wide range offindings in both animal and human studies.
For example, cholecystokinin (CCK) is secreted by the small intestine and is a
well-defined biomarker with high sensitivity and specificity with regard to appetite
and termination of feeding behaviors (de Graaf et al. 2004 ). However, it has little
effect on subjective feelings of fullness and subsequent frequency of meals or total
daily food intake. Based on a meta-analysis, de Graaf et al. ( 2004 ) report that,
depending on the administered dose of exogenous CCK, subject characteristics and
other experimental factors, intake suppression varied from 0 to 63%, and the effect
on subjectively rated appetite were apparent in only 8 of 17 studies. Ratings fre-
quently use categorical scales and visual analog scales (VAS) in which a subject
indicates a sensation by placing a mark on a horizontal line scale anchored at either
end with the extremes of the subjective feeling to be quantified, e.g.,‘not at all
hungry’and‘as hungry as I have ever felt’(Livingstone et al. 2000 ). A number of
factors may have a role in biasing responses regarding appetite.
Since humans evolved eating and energy regulatory mechanisms in environ-
ments where food intake was often limited and food excess was rare, sensitivity to
signals that initiate eating and continued eating would have had greater adaptive
value than those that terminated eating or satiation (Armelogos 2010 ; Lieberman
2006 ; Power and Schulkin 2009 ). These responsive mechanisms continue to
operate today in vastly different environments for most humans. The obesogenic
environment is replete with food cues that trigger and motivate the upregulation of
eating and may downregulate sensitivity to internal appetite cues of satiation and
satiety. Signals are also modified by energy balance, with many studies demon-
strating that the positive energy state of obesity reduces the response to leptin,
CCK, and other anorexigenic hormones and peptides. A state of negative energy
balance increases the response and subsequent eating behavior (Power and Schulkin
2009 ). That is, hunger and responsive hyperphagia are more sensitive to a negative
energy balance than the suppression of eating is to a positive energy balance.
Perception of visual and olfactory food cues initiates cephalic-phase responses,
that in turn set in motion endocrine cascades directly or indirectly regulating food
intake by increasing meal size, eating duration and the efficiency of digestion,
absorption, and metabolism (Power and Schulkin 2009 : 227). Learning (and
Pavlovian conditioning); experience; and social, cultural, and food-related envi-
ronmental factors trigger and mediate these responses. These adaptive
cephalic-phase responses are physical (e.g., gut motility increases), secretory (e.g.,
salivary and gastric peptide hormones are secreted), metabolic (e.g., thermogenesis
is increased). In concert, they play a role in the initiation of eating, sensory per-
ceptions of food and affect (Power and Schulkin 2009 ).
Table10.2lists some of the known cephalic-phase responses, the organs, or
tissues activated in these responses and their function. Systemically, energy
metabolism increases and, in preparation for the ingestion and digestion of food, the
10 Objective and Subjective Aspects of the Drive to Eat in... 211