The human appetite system is deeply linked to body composition and therefore to obesity (41).
The role of appetite in obesity has a long research history rooted back to 1968 when a series of experiments demonstrated that adults with obesity compared to normal weight eat more highly palatable foods but showed no difference in intake of standard foods (6). Appetite forms a bridge between the internal and external environments and therefore has both biological and behavioural or psychological aspects (41). By definition, appetite is the system that informs patterns of eating behaviour (6, 41). There are two forms of signals involved in appetite regulation (6, 42). The first form, episodic signals, are mainly inhibitory and usually generated by episodes of eating (42).
The second form, tonic signals, arise from adipose tissue stores and indicate the level of fat storage (6).
Episodic signals inform the brain about the amount of food ingested and its nutritional content via input through the senses to contribute to the termination of an eating episode and subsequently influence the strength and duration of the suppression of eating after a meal (6, 42). Following ingestion, specialized chemo- and mechano-receptors that are located within the gastrointestinal tract pass information to the hypothalamus in the form of gut hormones released in the stomach and intestines such as cholecystokinin (CCK), peptide YY (PYY), and glucagon-like peptide-1 (GLP-1) (6, 43). In the post-absorptive phase, after the nutrients have been digested and crossed
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the intestinal wall into circulation, they metabolize in peripheral tissues or organs which constitute satiety signals (6). In addition, the products of digestion and their respective metabolites reach the brain where they can bind to specific sites of action which influence neurotransmitter synthesis that informs the brain about the metabolic state resulting from food consumption (6). These signals underlie fluctuations in subjective feelings of appetite which mediate the termination of an eating episode as well as the strength and duration of inhibition overeating following a meal (6).
Generally, while hunger is suppressed by episodic signaling, it arises through tonic signaling and the overall strength of the drive to eat is the balance between these physiological processes (43).
Leptin and insulin are important tonic signals of long-term energy stores (6). They bind to receptors in the hypothalamus to inform energy balance by altering food intake (6). During periods of food deprivation, tonic signaling declines as reduced leptin and insulin signals reach the hypothalamus (6). This lowers sensitivity to episodic satiety signals causing an imbalanced homeostatic regulation resulting in a need for energy intake to generate a sufficient satiation signal to inhibit an eating episode (6). Ghrelin illustrates the characteristics of both an episodic and tonic signal in appetite control (42, 43). Endogenous ghrelin levels appear responsive to nutritional status and ghrelin acts as a compensatory hormone (42). Although there is individual variability in hormone secretion, this means that in obese people ghrelin levels would be reduced in an apparent attempt to restore a normal body weight status and with weight loss, ghrelin levels would rise to promote the feeling of hunger (42). This is likely to be one of the signals that make the loss of body weight so difficult to maintain, therefore appetite regulation is highly important when it comes to weight loss strategies (42).
If eating behavior were only regulated by these homeostatic systems, food consumption would simply be a response to a purely physiological need, and the great majority of people would easier manage to keep normal body weight (44). However, the regulation of appetite in humans is much more complex as the homeostatic control of food intake is strongly influenced by
hedonistic impulses, the reward system, and eating experiences (44). The hypothalamus controls both the homeostatic and non-homeostatic regulation of appetite (44). Pre-prandial motivation is where diminished satiety signals are detected in the gut by hypothalamic areas which respond by increasing the drive to consume (6). The activation in hypothalamic areas results in cephalic
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phase responses (6). These are anticipatory responses generated in many parts of the
gastrointestinal tract when exposed to the sensory properties of food like sight and smell which aim to optimize the metabolism of ingested nutrients (6, 42). The senses provide input via peripheral receptors to the primary sensory cortices which are integrated with information about motivational subjective state and memory to influence behaviour (6). Food hedonics is comprised of important motivational components which represent the sensory and cognitive processes involved in the experiences of ‗liking‘ and ‗wanting‘ (6).
Historically, hedonic processes have been viewed as a function of the nutritional need-state. In a state of depletion, the hedonic response to energy-providing foods is enhanced and when replete, the hedonic effect of these foods is reduced (42). However, such hedonic reward pathways can override the homeostatic system and increase the desire to consume, despite physiologic satiation and replete energy stores (45). It is important to make the distinction between biological drive and implicit wanting as separate, but interacting entities (43). Consumption of standard food generates information on its energy content and taste in the brain stem (42). This information is transmitted to the hypothalamus leading to an up-regulation of various satiety peptides, causing consumption to cease which can be shown in figure 3 (6, 42).
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However, with ingestion of palatable food, information is transmitted to the reward circuit, leading to the greater release of reward mediators like dopamine, endocannabinoids, and opiates (6, 42). In turn, this causes increases in hunger peptides such as neuropeptide Y (NPY) and orexins and decreases the signalling in satiety peptides such as insulin, leptin, and CCK (6, 42).
Therefore when food is highly palatable, the drive to eat is maintained, with continued eating now mediated by reward mechanism rather than biological need (6, 42).
To better understand the integration of these behavioral and sensory elements with physiological factors for appetite regulation, a conceptual scheme called the Satiety Cascade was proposed over 30 years ago by Blundell et al which the adapted form can be seen from figure 4 (43, 44).
Sensory elements induce appetite before food intake as a preparatory act (44). Hunger, defined as the physiological sensation generated in response to a biological need for energetic nutrients, drives food intake (44). After eating has been initiated, there is satiation or fullness, which is the process that triggers a series of signals which lead to meal termination (43, 44). Lastly, satiety is the process that leads to the post-meal suppression of hunger, hence, inhibition of further eating (43). In sum, hunger is conceptualized as part of a broader system of appetite control (43). The rise and fall of hunger during the day drive patterns of food intake (43). Satiation occurs during the act of eating, and satiety determines the time-lapse between meals (44). All these hedonic