| The appetite is the desire to eat
food, felt as hunger. It exists in all higher
lifeforms, and serves to regulate adequate energy intake to maintain metabolic
needs. It is regulated by a close interplay between the digestive
tract, adipose tissue and the brain. Dysregulation of appetite contributes to anorexia
nervosa and cachexia on one side, and obesity on the other side of the spectrum.
Regulation
The regulation of appetite has been the subject of much research in the last
decade. Breakthroughs included the discovery, in 1995, of leptin, a hormone that appeared to provide negative feedback. Later studies showed that appetite regulation is an
immensely complex process involving the gastrointestinal
tract, many hormones, and both the central and autonomic
nervous systems.
Effector
The hypothalamus, a part of the brain, is the main regulatory organ for
appetite. The neurones that regulate appetite appear to be mainly serotinergic, although neuropeptide
Y (NPY) and Agouti-related peptide (AGRP) also play a vital role. Hypothalamocortical and hypothalamolimbic
projections contribute to the awareness of hunger, and the somatic processes controlled by the hypothalamus include vagal tone (the activity of the parasympathic autonomic nervous system), stimulation of the thyroid
(thyroxine regulates the metabolic rate), the hypothalamic-pituitary-adrenal axis
and a large amount of other mechanisms.
Sensor
The hypothalamus senses external stimuli mainly through a number of hormones such as leptin, ghrelin, PYY 3-36,
orexin and cholecystokinin;
all modify the hypothalamic response. They are produced by the digestive tract and by adipose tissue (leptin). Systemic mediators, such as tumor necrosis factor alpha (TNFα), interleukins 1 and 6 and corticotropin-releasing hormone (CRH) influence appetite negatively; this mechanism
explains why ill people often eat less.
In addition, the biological clock (which is regulated by the
hypothalamus) modifies hunger. Processes from other cerebral loci, such as from the limbic system and the cerebral cortex, project on
the hypothalamus and modify appetite. This explains why in clinical depression and stress,
energy intake can change quite drastically.
Role in disease
Dysregulation of appetite lies at the root of anorexia nervosa,
bulimia nervosa and binge eating disorder. In addition, decreased response to satiety may promote development of obesity. Various hereditary forms of
obesity have been traced to defects in hypothalamic signalling (such as the leptin receptor and the MSH-4 receptor).
Pharmacology
Mechanisms controlling appetite are a potential target for weight loss drugs. Early anorectics were fenfluramine and phentermine. A more recent addition is sibutramine (Reductil®, Medaria®), which
increases serotonin and noradrenaline levels in the central
nervous system. In addition, recent reports on recombinant PYY 3-36 suggest that this agent may contribute to weight loss by suppressing appetite.
Given the epidemic proportions of obesity in the Western world, developments in
this area are expected to snowball in the near future, as dieting alone is ineffective in most obese adults.
Further reading
- Neary NM, Goldstone AP, Bloom SR. Appetite regulation: from the gut to the hypothalamus. Clin Endocrinol (Oxford)
2004;60:153-60. PMID
14725674.
- Wynne K, Stanley S, Bloom S. The gut and regulation of body weight. J Clin Endocrinol Metab 2004;89:2576–82.
PMID
15181026.
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