They say that the key to a man’s heart is through his stomach. A more biologically accurate metaphor would be that your gut holds several keys—not to your heart, but to your brain. Remarkably, the gut is capable of altering the brain’s ability to process sensory information and generate behavior. This is achieved through the release of gut hormones into the bloodstream, which then enter the central nervous system and alter brain activity. Thus, contrary to popular belief, the brain and body are not isolated from one another by an inseparable barrier; they are engaged in an exquisitely regulated dialogue in order to serve the needs of the organism as a whole.

Animal brains have the amazing ability to take in massive amounts of sensory information, filter out unimportant information, and generate the appropriate behavioral response. We normally think about how the brain processes sensory information coming from the outside world, but it is also constantly sifting through signals generated from within the organism. While our eyes, ears and other sense organs relay information to the brain about what is happening externally, a variety of signals generated in the body relay information about what’s happening internally. For example, various metabolic signals—including molecules like glucose and insulin—convey information about the body’s needs to the central nervous system. This type of brain-body interaction regulates how hungry or sated (“full”) we feel, ultimately promoting behaviors that will satisfy these needs. In this way, “the wisdom of the body” helps make sure that the organism acts in order to maintain a proper internal balance, or homeostasis [].

Secreted gut hormones affect the brain and behavior

The two most famous hormones involved in regulating hunger and satiety are ghrelin and leptin (see [] for a helpful graphic). The stomach secretes ghrelin when the body needs caloric energy. Injecting ghrelin into laboratory animals elicits food-seeking behavior; when administered intravenously, people report feeling hungry even when they’re full. Neuroimaging studies have shown that gut hormones like ghrelin change the way that the brain responds to sensory information, especially when it comes to food []. In one experiment, participants had to fast overnight before eating a controlled breakfast, prior to entering a brain scanner. Once inside, they were shown pictures of both food and non-food items while baseline measurements were taken. They were then given either the hunger-promoting hormone ghrelin or saline (which has no effect on hunger) and shown a new set of images. Importantly, participants didn’t know which injection they were receiving. The result: subjects who received ghrelin injections displayed enhanced responses in brain regions implicated in reward processing and motivation, but only in response to food images. This suggests that particular bodily needs can affect brain activity specifically in response to stimuli that are relevant to those needs. The basic idea, which is supported by work in laboratory animals, is that states of hunger induced by hormones like ghrelin alter reward processing in the brain in a way that motivates them to seek a specific type of item in their environment: food.

In contrast to ghrelin, the gut-derived hormone leptin is secreted from fatty tissue and acts as a satiety signal. Basically, it’s the body’s way of telling the brain, “We’re full now. Stop looking for food.” Animals lacking the gene encoding leptin or its receptor display voracious feeding behavior and develop morbid obesity (Figure 1). Leptin is actively transported into the brain and affects brain cells directly. Animals with diet-induced obesity display leptin resistance, analogous to the insulin resistance associated with type II diabetes []. This means that the body is no longer responding normally to the increase in circulating leptin that follows a meal. When scientists deliver leptin directly into the brain, however, the same animals show normal responses (decreased feeding behavior). This suggests that diet-induced obesity may lead to defective transport of these hormones into the brain. In other words, the body can no longer communicate with the brain in order to generate an appropriate behavioral response: “Stop eating!”

Figure 1: Compared to the normal mice (right), leptin-deficient mice (left) exhibit excessive food consumption and diet-induced obesity. Image from Wikimedia Commons.

The direct application of gut-derived hunger and satiety hormones into the brain has demonstrated that these molecules probably play a role in a variety of brain processes. These include not only the regulation of food-seeking behavior, but also reward processing, neurogenesis, and learning and memory. While the effects of peripheral gut hormones on such a wide array of brain functions may seem peculiar at first, it begins to make sense when you consider how cognitively and behaviorally demanding finding food is for animals in the wild. The wide range of effects that hormones like ghrelin and leptin have on central nervous system function also has potential clinical relevance; it suggests that treatments aimed at fighting obesity through disruption of ghrelin secretion may have side-effects beyond fat storage and metabolism [].

Associative learning and the motivation to eat: implications for obesity

A variety of eating and metabolic disorders, including obesity and diabetes, have become increasingly prevalent in countries such as the United States (and increasingly elsewhere []). Diet-induced obesity predisposes individuals to a variety of other health problems (Figure 2), and imposes a huge economic burden on society []. One potential explanation for why this has happened is that, in places with an abundance of highly palatable foods, our caloric needs are usually satisfied, and feeding behavior is motivated predominantly by hedonic (“I like this”) rather than homeostatic (“I need this”) factors. Calorie-dense, nutrient-poor foods are readily available, and we are frequently bombarded with the sights and sounds of logos and advertisements that we have learned to associate with food “rewards.” Based on the way our brains are wired to learn by association, these food-predicting sensory cues come to induce hunger and cravings even when our caloric needs are already satisfied.

Figure 2: Diet-induced obesity predisposes individuals to a wide variety of medical complications. Image from .

Learned associations between food and non-food items can trigger highly specific feeding behavior. For example, rats can be trained to associate a simple stimulus, such as a tone, with a food reward. Repeated presentations of a tone with a specific food results in a phenomenon known as ‘cue-induced feeding.’ After animals learn to associate the tone with a food reward, subsequent presentations of the tone by itself induce food-seeking behavior, even in fully fed rats []. In addition, presenting the cue while the rats are eating causes them to consume more than they would in the absence of the tone. (It isn’t difficult to imagine a similar phenomenon at work when we encounter the sights, sounds, or smells associated with our favorite fast food restaurants.) Intriguingly, this effect is specific to the food that was associated with the tone. When presented with a different type of food, rats do not eat more in the presence of the cue. Thus, a simple sensory stimulus can elicit what appears to be a highly specific food ‘craving.’ Not surprisingly, the food industry takes advantage of the natural tendency of our brains to make sensory-specific associations when it produces and markets many of the foods we eat (see [] for a short video on this subject).

With the near-constant barrage of sensory cues signaling the presence of easily accessible and highly rewarding food items, is there any hope of curbing the growing epidemic of diet-induced obesity and metabolic disorders? One approach is to emphasize and promote simple life strategies that help reduce overeating. This includes everything from getting adequate sleep [] to making a conscious effort to gauge whether or not the desire to eat is the result of a true bodily need or is merely “sensory hunger” []. Another idea that is only just beginning to be explored by researchers is to develop therapies that affect the brain’s responsiveness to food cues. By understanding how hunger and satiety signals such a ghrelin and leptin enter the brain and affect its activity patterns, we may be able to develop drugs that alter or block this effect in a way that reduce food-seeking behavior in response to sensory cues (such as advertisements). Again, this line of research is in its infancy. At the very least, though, this should serve as some savory food for thought.

Nick Jikomes is a Ph.D. candidate in Neuroscience at Harvard University.


[] Rodolfo K. What is homeostasis? Scientific American. (January 3, 2000).

[] Bland J. The Collateral Damage of Insulin Resistance. Huffington Post. (March 19, 2013).

[] Reinberg S. Procedure Lower ‘Hunger Hormone’ to Help Obese Lose Weight. U.S. & World News Report. (March 7, 2013).

[] Mukhopadhyay A. Muddled thinking is fuelling obesity epidemic. South China Morning Post. (March 10, 2013).

[] Begley S. The Costs of Obesity. Huffington Post. (April 30, 2012).

[] Crowe K. Food cravings engineered by industry. CBC News. (March 6, 2013).

[] Harmon K. How Slight Sleep Deprivation Could Add Extra Pounds. Scientific American. (October 24, 2012).

[] Somov P. Sensory-Specific Satiety: Thrills of the Tongue & Fullness. Huffington Post. (April 16, 2009).

Technical references

[] Malik S., McGlone F., Bedrossian D., Dagher A. Ghrelin modulates brain activity in areas that control appetitive behavior. Cell Metabolism. (2008). 7:400-409

[] Larder R. & O’Rahilly S. Shedding pounds after going under the knife: Guts over glory—why diets fail. Nature Medicine. (2012) 18:666-667

[] Petrovich G.D. Learning and the motivation to eat: Forebrain circuitry. Physiology & Behavior. (2011). 4:582-589

For further reading

“Reducing Your Risk of Obesity.” Ricker Polsdorfer, MD. Beth Israel Deaconess Medical Center.

The Obesity Prevention Source. Harvard School of Public Health.

Beth Israel Deaconess Medical Center Division of Endocrinology

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