7. Food Intake Regulation

Subchapter content:

1. Introduction into food intake regulation
2. Appetite control


Introduction into food intake regulation

Food intake disorders are very common in modern population. Most of them are linked to serious pathophysiological consequences, impairing functions of all major systems. There is a vivid discussion in scientific community concerned about prevention and treatment of these diseases.

Generally speaking about 80 % of patients suffering from food intake disorder have at least one more comorbidity. Therefore every medical professional should know basic principles of neuroendocrine control exercised over the feeding, should be able to recognise patterns in presented imbalance and provide accurate treatment.


Appetite control

Let us revisit one of the earliest theories in the field. So called glucostatic theory is well outdated today and was recently replaced by more accurate and complex one. But it still provides some insight into the presented problem.

According to glucostatic theory the hunger is initiated by decline of blood glucose level. Transient hypoglycaemia is recognised by specialised cells in so-called hunger centre localised in lateral hypothalamic area (LHA), stimulating feeding behaviour which is consciously perceived as hunger. On the other hand postprandial hyperglycaemia stimulates neutrons of “satiety centre” in venture medial hypothalamus (VHM). Increased activity of VHM then inhibits activity in LHA, resulting in cessation of feeding behaviour.

As clear as glucostatic theory is, the case is much more complicated. Recent studies have shown that glucose blood level participate in appetite control only if severe energy deprivation is presented. In fact the most important regulators of food intake are social, cultural and psychological factors. These factors may as well result in increased food intake: hyperphagia or decreased food intake: hypophagia. We would like to stress not to underestimate importance of social, cultural and psychological factors. Medical professionals should appreciate complex neural and endocrine processes underlying them. Biochemical control is exercised mainly over feeding termination.

No matter how complex interactions which our theories describe are, no matter how hard seizable it may seems at first glance, the role of hypothalamus and it’s area remain crucial.

At every moment hypothalamus processes large amount of signals, which can be divided into two separate categories:

a) appetite stimulating – orexigenic

b) appetite inhibiting – anorexigenic

Orexigenic as well as anorexigenic signals can be further classified according to their place of origin as peripheral or central.

Role of arcuate nucleus

One of the most important structures in hypothalamus involved in regulation of food intake is called arcuate nucleus. It contains neurons producing orexigenic substances as well as anorexigenic ones.

Substance called neuropeptide Y (NPY) is one of the most important peptides produced in arcuate nucleus. It acts as potent orexigenic signal. Axons of neurons, which produce NPY, travel to LHA, where they stimulate secretion of MCH (melanin-concentrating hormone). MCH acts as orexigenic signal as well as NPY. The orexigenic pathway is triggered while there are insufficient inhibition signals or right psychological and social factors are presented. It results in urge to feed – hunger.

Proopiomelanocortin (POMC) is most potent anorexigenic signal originating in arcuate nucleus. Neurons producing POMC synapses in LHA as well as neuropeptidic neurons from previous paragraph. The difference is that they stimulates neurons secreting wide variety of anorexigenic substances – most of them should be fairly common to you – corticoliberin (CRH), thyrotropic hormone (TRH) and oxytocin. Their production is also potentiated by an increase in so called adiposity signals. Adiposity signal is any substance which apart from its role in signaling pathways also posses role in metabolism of adipose tissue. We will talk about them in detail at the end of this chapter. POMC pathway produce feeling of satisfaction linked with feeding cessation.

Satiety signals

By satiety signals we mean group of substances produced in gastrointestinal tract, which regulates feeding on immediate basis. According to this statement we can classify them as peripheral anorexigens. As the name hints this group produce feeling of satiety and leeds to feeding cessation. The theory states that a nutrients passing through lumen of GIT activate secretion of many different satiety signals. These signals stimulates endings of autonomous nervous system. Its fibers terminate in solitary tract nuclei, localized in brain stem. Neurons from solitary tract then distributes information about current state to hypothalamus.

Now we will discus cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) in greater detail. But there are many more satiety signals for example: bombesin, amylin, somatostatin, enterostatin etc..

Cholecystokinin (CCK)

CCK is produced by duodenal and iliac cells. Stimuli for its secretion are luminal stretch and biochemical changes linked to food passage. Its’ name is derived from ability to cause contractions of gallbladder.

CCK binds to receptors localized on vagal nerve called CCK-1Rs. Activation of these receptor causes satiety. Precise pathway involving solitary tract is described higher.

Glucagon-like peptide-1 (GLP-1)

GLP-1 is another satiety signal produced by food passage through lumen of gut. It acts as peripheral anorexigen in same manner as CCK. But beside this role, it also stimulates insulin release from pancreas by potentiating glucose effect on from Langerhans’ islets. GLP-1 also inhibits glucagon secretion.

Increased GLP-1 blood level leads to decreased food intake. And this attribute of its led scientific community to consider GLP-1 as promising medication for management of diabetes and obesity. Its clinical plausibility is greatly limited by its short biological half time of 1 to 3 minutes. But inhibitors of its degrading enzyme (dipeptidyl peptidase IV) or GLP-1 analogs resistant to degradation were introduced instead.


Ghrelin is special at least in many ways. It is the only one GIT peptide known so far exhibiting orexigenic activity. So we can describe it as peripheral orexigen. It is produced by glandular cells of stomach known as “A-X” cells. Ghrelin secretion is potentiated by contractions of stomach if its lumen is empty. But some ghrelin secretion can be traced to placental, renal, cardiac and thyroidal cells as well.

Its orexigenic activity is exercised by bigger food portion rather than more frequent feeding. Hunger can be observed after introducing larger dose of ghrelin intravenously.

In healthy adult ghrelin concentration can reach as high as twice its median few minutes before feeding and decrease to half its median postprandially. However note that in anorectic patient ghrelin blood level is permanently elevated and it is decreased in diabetics. This can only be clarified by loss of its physiological action under these pathological conditions.

Adiposity signals


Leptin is substance produced by adipose tissue and its main role rests in adaptive regulation of metabolism according to nutritional status. If the leptin signal is weak, catabolic processes are inhibited and production of NPY in arcuate nucleus is increased. Thus energy expenditures diminish and subject carves for food. May the leptin signal be strong, POMC neurons in arcuate nucleus are stimulated and satiety is achieved. Anorexigenic effect is stronger than orexigenic. This can be demonstrated by severe hyperphagia and obesity, when leptin receptors are mutated or disorder in leptin synthesis is presented. But both disorders are very rare in humans.

In obese patients leptin level is elevated, but hormone does not exercise any physiological activity. This phenomenon is called leptin resistance.


Insulin is a hormone produced by B-cells of Langerhans’ islets of pancreas. Its physiological importance is covered in great detail in Subchapter 11/7. It role in food intake is as follows: insulin increase activity of POMC neurons localized in arcuate nucleus, thus exhibiting strong anorexigenic effect. Insulin deficiency (for example in diabetes type I) is linked with enhanced activity of NPY neurons. But there is sufficient evidence that it exercises anorexigenic effect only under physiological conditions. It role in food intake diminish in disease.

Subchapter Authors: Patrik Maďa and Josef Fontana