To say that humans eat when they are hungry and stop when they are full is not very helpful and frequently wrong. The current epidemic of obesity strongly belies the notion that we stop when we have eaten enough, particularly if palatable (sweet, fatty, calorie dense) foods are available. In anorexia nervosa, patients experience intense feelings of hunger, but respond with massive resistance to eating. When one considers that in the US $465 billion is spent on restaurant dining each year, and that 'eating out' is ranked second out of all expenditures on non-durable goods (and in the top 10% of all household spending) , food appears to be its own 'reward', providing pleasure and satisfaction separate from its nutritional value. If we used an automobile as an analogy, we can experience car in terms of its function, e.g. transportation (Honda Civic) or a thrill ride (Ferrari).
Throughout much of the twentieth century, scientific inquiries into feeding behavior focused on finding the hunger center, and its opposite, a satiety center. This research was initially stimulated by the observations that patients with certain tumors of the pituitary gland (a hormone regulating structure at the base of the brain that we discuss in more detail later) became morbidly obese. It suggested that the pituitary gland or neighboring structures of the brain were central to appetite regulation.
The focus for research shifted dramatically in the 1990's with the discovery that certain genetic forms of obesity in animals and humans were caused by a deficiency of a specific hormone (chemical regulator) later named leptin. Leptin is produced outside the brain, by fat tissue. With the realization that factors outside the brain exerted important regulatory influence over weight, scientific focus shifted from appetite regulation, to regulation of energy and body weight.
The following sections review our evolving knowledge about the interacting networks connecting the brain to the rest of the body to control food intake and body weight. A number of excellent reviews by Broberger 2005, Fride et al 2005, Kishi and Elmquist 2005, Cupples 2005, van der Lely 2004, DeNino et al 2003, Funahashi et al 2003, Cowley 2003, Elquist et al 1999, and Woods 1998 provide much of the basis for this chapter. A glossary appears at the end of the chapter as both reference and review.
How Does Your Brain Know What You've Been Eating
A prominent role for the brain, and in particular the hypothalamus, in the regulation of feeding behavior was established more than fifty years ago but how the brain exerts control over weight and eating did not begin to be understood until the 1990's. As any parent of a teenager will tell you, you can't control them, if you don't know what they're doing. The same can be said about the brain and food. In order for weight to remain stable over time, there has to be a way for the brain to learn "what's going on". It has been shown that the brain receives overlapping chemical and electrical signals to help regulate food intake and energy expenditure. The following sections describe these inputs.
The Vagus Nerve. When you eat, a range of information about the taste, texture and distension of the gut is sent from the gastrointestinal tract to the brain as an electrical signal via the vagus nerve. (Some readers may be familiar with the important role the vagus nerve serves in the autonomic nervous system where it carries signals from the brain to body organs governing such important functions as heart rate, respiration, pupil dilation and gut motility.) The vagus nerve collects information on the nutrients in the gut as well as the presence of local hormones that are released into the gut during feeding. The information collected is integrated by the vagus nerve and sent from the gut to the nucleus tractus solitarius (nTS) in the brain stem. Thus, the vagus nerve is the 'hard wired' channel for communicated food information to the brain.
Insulin. A number of chemicals (hormones) released in the periphery (outside the brain) send information to the brain about our energy balance. During a period of fasting blood sugar (glucose) levels fall (hypoglycemia). The drop in glucose stimulates food intake. As you eat, the hormone insulin is released in response to increases in blood sugar. Throughout the body, organs depend on insulin to facilitate the transport of glucose from outside cells to inside cells and as insulin is released blood glucose levels fall. In addition to its role in regulating glucose levels, insulin also directly decreases appetite and this effect appears to be independent of changing blood glucose levels. Thus, insulin has both indirect (via glucose) and direct effects on appetite regulation.
Leptin. Leptin is a hormone that is produced by adipose (fat) tissue and released into the blood stream where it travels to the brain. In animals and humans a genetic deficiency in producing leptin causes hyperphagia (overeating) and morbid obesity as well as changes in the regulation of other hormones. Leptin exerts its effects both in the brain and in peripheral tissues. In the brain it inhibits food intake and in the rest of the body it is associated with increased energy expenditures. Weight loss associated with leptin appears to be due entirely through a loss of fat.
Ghrelin. Ghrelin is produced is a hormone produced in the stomach and gastrointestinal tract in response to hunger. Both acute fasting and chronic fasting increase ghrelin levels and when ghrelin is given either in the blood or the brain it increases feeding and leads to increased body weight. Dieting associated weight loss causes ghrelin levels to rise inversely to body weight and body fat.
Cholecystokinin (CCK). This gut peptide is released in response to feeding. In both animals and humans CCK causes a dose dependent decrease in meal size. It is one of several satiety peptides.
Peptide YY. This gut hormone is released in the circulation and signals the hypothalamus that there are lipids (fats) and carbohydrates present in the small intestine and colon. Experimental administration of PYY inhibits food intake and contributes to weight loss.
Oleoylethanolamide. The observation that marijuana smoking causes acute food cravings stimulated research into the question endogenous (produced by the body) cannabinoids (drugs that act on the same receptors as marijuana) which are produced throughout the nervous system may play a role in regulating appetite. Oleoylethanolamide (OEA) is a fatty acid that is produced in the small intestine and is chemically similar to cannabinoids. Acting on the vagus nerve, OEA decreases body weight by increasing the time between meals and increases energy expenditure.