Hunger, Physiology of
HUNGER, PHYSIOLOGY OF
HUNGER, PHYSIOLOGY OF. Hunger is the set of internal experiences that lead a human or animal to seek food. Appetite describes the preferences that surround the selection of food that is found. For many people, hunger is a set of feelings often focused on the stomach. It may be associated with contractions of the stomach or intestine, and described as "emptiness." Indeed, many of the early ideas about hunger and its opposite, satiety, were described in terms of stomach contractions or stomach distension. Increased physiological understanding has yielded the information that the stomach and intestine are only one part of the system experienced as hunger.
A drive to eat food can be produced by damage to selected parts of the brain, usually located in the hypothalamus near the pituitary. When this area is damaged, animals and humans become voracious eaters and become obese. This indicates that there are sections of the brain that can inhibit food intake that, when destroyed, fail to do this. Alternatively, there are other regions of the brain (lateral hypothalamus) where damage in either humans or animals produces reduced food intake and wasting.
The connections between what happens in the body and how the brain recognizes it have advanced by leaps and bounds since the 1970s. One of the first discoveries was that many of the same messages or signals that are found in the stomach and intestine are also found in the brain. These so-called gut-brain messages can serve to stimulate or inhibit feeding. As a general rule, the ones produced and released in the body tend to inhibit feeding. Thus cholecystokinin, a hormone that causes the gallbladder to contract, also inhibits food intake. This peptide works both in the body and when put into the brain. Another gut-brain hormone is ghrelin. In contrast to cholecystokinin, ghrelin stimulates food intake whether injected into the body or into the brain. The fat cells are another source of important signals for hunger. The most important of these sources is a hormone called leptin. When this hormone is absent in either humans or animals, massive obesity results. When this hormone is given back, hunger immediately subsides, indicating the important role that this hormone plays in the control of hunger. The amount of leptin released from fat cells increases as the total body fat increases. It thus serves as a circulating marker for the level of fatness. Once in the circulation, leptin acts on the brain. Through a lock-andkey mechanism, leptin changes the formation of four other hormones in the brain that regulate eating. When leptin is high, the release of two peptides (neuropeptide Y and agouti-related peptide) in the brain is reduced and two other hormones (cocaine-amphetamine regulated transcript and proopiomelanocortin) are released. Acting in concert, this combination of hormones reduces feeding and relieves the sensations of hunger. Conversely, when leptin is low, the opposite situation occurs, and hunger develops along with the search for food.
Insulin is a second major hormone in the body that signals hunger. In diabetic patients who take insulin and tightly control their blood sugars, mild degrees of obesity frequently develop. Similarly, some of the drugs for treating obesity (sulfonylureas and peroxisome proferator-activated receptor-γ agonists) produce weight gains. One likely way this happens is through reducing blood glucose that in turn signals the need for food.
The role of circulating glucose in the initiation of hunger has been advanced considerably. Beginning with studies in animals, it was found that a small drop of about 10 percent in glucose preceded the onset of many but not all meals. When this drop in glucose was prevented, the animal did not eat at the expected time. That is, hunger had been prevented by manipulating glucose. The glucose-stimulated hunger can be provoked by giving a drug that mimics the key nerve (vagus) that supplies the pancreas to release insulin. Studies in human beings also found that a small drop in glucose preceded many meals. It has been long known that there were lock-and-key systems in the brain responding to glucose or its deficiency. The experiments described above suggest that the brain signals a small release of insulin that leads to a transient decrease in glucose, which in the "primed" animal produces an internal feeling of hunger.
These many signals for feeding can increase the intake of all available foods, or they can signal intake of certain foods. We know that when we have eaten our fill of turkey at Thanksgiving, there is still room for pumpkin pie or ice cream. The loss of hunger for one food after it is eaten is known as sensory specific satiety, that is, the overall drive to eat can be regulated in parts. This is consistent with the finding that some of the signals described earlier stimulate one type of food intake or another, but not necessarily all. Thus, some signals are known that will specifically reduce the intake of fat and others, carbohydrate.
Obesity results from changes in leptin or damage to the brain. From studies on the control of feeding, it is known that at least two monamine neurotransmitters (norepinephrine and serotonin) in the brain play a particularly important role. These neurotransmitters have been the subject of considerable interest, since most of the medications used to treat obesity influence hunger through changing levels of one or both of these neurotransmitters. As more is learned about the control of hunger, a steady source of new targets is available that can be used to develop future medications for the treatment of obesity.
See also Acceptance and Rejection; Anorexia, Bulimia; Appetite; Eating: Anatomy and Physiology of Eating; Obesity; Sensation and the Senses.
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George A. Bray