11.2: Hunger - Theories, Detectors, and the Hypothalamus

Learning Objectives

1. Explain the concept of a set-point theory and how the detection of blood glucose levels and body fat explains some elements of feeding behavior.
2. Discuss the evidence for and against the existence of hypothalamic hunger and satiety centers.
3. Explain the effects of glucose, insulin, CCK, NPY, leptin, Ghrelin, and serotonin on eating behavior.

Overview

What determines when we are hungry - how is the need for food detected? How does the detection of a need lead to eating? And what determines when we stop eating? In this section we will explore potential hunger signals and various theories that explain some elements of eating behavior. As previously noted, human eating behavior is complicated by a wide array of environmental factors. As a consequence, much of our understanding of the biological factors involved in eating comes from animal studies.

Eating behavior is controlled by two separate, yet related, systems - one that signals a need to eat (i.e. hunger) and another that signals when that need has been met (i.e. fullness or satiety). In homeostatic terms, hunger is a complex "drive state" that involves multiple system variables and detector mechanisms. The key to the function of these systems may be located in specific hypothalamic nuclei. In addition, various chemical factors, including glucose, ghrelin, cholecystokinin (CCK), Neuropeptide Y (NPY), and leptin can act as systems variables which play key roles in eating behavior.

Hunger - The Drives Motivating Eating

Hunger is a classic example of a drive state, one that results in thoughts and behaviors related to the consumption of food. As we will see, hunger is often triggered by low glucose levels in the blood (Rolls, 2000), and behaviors resulting from hunger aim to restore homeostasis regarding those glucose levels. But various other internal and external cues can also cause hunger (Figure \(\PageIndex{1}\)). For example, when fats are broken down in the body for energy, this initiates a chemical cue that the body should search for food (Greenberg, Smith, & Gibbs, 1990). External cues include the time of day, estimated time until the next feeding (hunger increases immediately prior to food consumption), and the sight, smell, taste, and even touch of food and food-related stimuli. Note that while hunger is a generic feeling, it can also lead to the eating of specific foods that correct for nutritional imbalances we may not even be conscious of. For example, a couple who was lost adrift at sea found that they began to crave the eyes of fish. Only later, after they had been rescued, did they learn that fish eyes are rich in vitamin C - a very important nutrient that they had been depleted of while lost on the ocean (Walker, 2014).

We'll begin our exploration of ingestive behaviors with eating, the behavior motivated by hunger. While you might think the control of eating is quite simple, the regulated variables involved in eating are not so well described.

Figure \(\PageIndex{1}\): External cues, like the sight and smell of food, can ignite feelings of hunger. [Image: Marco Verch, https://goo.gl/c4TC5A, CC BY 2.0, https://goo.gl/BRvSA7]

Homeostatic Set-Point Theories

Before we look at the mechanisms that produce hunger, we'll first consider some of the major theories that strive to explain hunger and eating. There are many theories that we could consider and, perhaps, someday a single theory will emerge that is superior to all others, but at the present time we don't have a single theory that accounts for how all the different factors that impact feeding determine what we do. Most significantly, while human eating behavior tends to align with biological expectations over the long-term, the theories that focus on this fail to explain the increase in obesity that we see today (Speakman et al., 2011). In other words, there is a correlation between how much we eat (the calories we ingest) and how much we use (the calories we burn) when we consider our behavior over an extended period of time - but not when we look at individual meal-taking and daily eating behavior. (This example should remind you of the discussion of Homeostasis from the previous section of this chapter. If not, you should take a step back before continuing.)

You've probably been exposed to the notion of a body weight "set-point", the idea that you have an "ideal" weight and it takes a lot of work to move away from that set-point, that optimal value that our body strives to achieve. Perhaps we have some ideal level of energy that is necessary and that we eat to restore this value. In other words, perhaps we have a set-point for available energy. Is hunger an attempt to restore energy reserves and is hunger merely signaled when energy reserves are depleted? This would predict a consistency in energy use and food intake that we simply do not see (Hall et al., 2021).

Hunger & Glucostatic (Glucose Utilization) and Lipostatic (Fat Levels) Theories

What makes you feel hungry or full? Do you feel hungry when your stomach is empty? Do you feel satisfied when your belly actually feels full? How does the stomach tell the brain that nutrients are there? Interestingly, a stomach full of food will still put a stop to feeding, even if there are no nerves connecting it to the brain. And a full stomach - with no nutrients present - can also end feeding. These are just some of the interesting questions and phenomena that suggest the complexity of the signaling involved in hunger and satiety (fullness).

It turns out that the brain responds to two types of hunger signals:

• Short-term. Receptors in the liver and the brain are involved in responding to short-term signals. For example, they respond to levels of available fuel (i.e. the sugar, glucose) among other messages in the blood.
• Long-term. Long-term hunger signals are a consequence of the monitoring of fat stores. When fat cells are full, they produce a hormone called leptin. Leptin then inhibits the brain mechanisms that control eating - leptin makes the brain less responsive to short-term signals. Leptin effectively turns hunger signals off (negative feedback).

Perhaps the maintenance of blood glucose (readily available fuel in the blood) could be what controls feeding for the short-term and the maintenance of body fat (stored energy) could provide a long-term explanation of eating behavior. These are both variations on the set-point theory. While each of these theories has its problems, they are consistent with some findings.

Glucostatic theories propose that we work to maintain some ideal level of blood glucose. In contrast, lipostatic theories propose that we monitor the level of body fat that we have stored and then alter our eating to compensate when fat levels are not at the desired level. Having identified what is being regulated (our system variable, blood glucose or body fat) and presuming some set point, are there detectors to monitor our regulated variables?

Consistent with glucostatic theory, the usual trigger for hunger is a drop in blood glucose (hypoglycemia). We can artificially trigger short-term hunger, by one of two mechanisms:

• Decrease blood glucose with the administration of insulin. This causes available glucose to be stored and used by body cells. Recall from the previous section on digestion that the increase in insulin during the cephalic phase of digestion can increase your pre-meal hunger.
• Inject 2-deoyglucose (2-DG). 2-DG is structurally similar to glucose, but cells are unable to metabolize it. This produces glucoprivation - although glucose is available, cells are unable to use it. Both body and brain cells are deprived of glucose.

Both manipulations above deprive body cells of glucose and both will produce eating, consistent with a glucostatic hypothesis (Thompson & Campbell, 1977). Please see the next section of this chapter on digestion mechanisms for more details on the interaction between glucose and insulin and their role in hunger..

Lipostatic theory proposes that when stored fat drops below an optimal value, hormones are secreted that increase food intake and promote weight gain (Gale et al., 2004). It also proposes that when energy stores exceed that optimal value, adipose (fat) cells release leptin to reduce eating.

In addition to the relatively straightforward mechanisms of glucose and fat signals, there are a multitude of other neural and digestive inputs that can modulate our eating behavior.

Hunger, Satiety, and the Role of Gut Peptides

The stomach and other parts of the gastrointestinal tract produce peptides that can function as hormones, traveling in the blood stream to their site of action. One peptide that has been studied quite extensively is cholecystokinin (CCK). In the absence of a neural connection, a chemical in the blood would be an ideal mechanism for the stomach to use to communicate with the brain. It turns out that CCK does cause food-deprived rats to eat smaller meals - but is that because they are feeling satiety? It turns out that CCK can make one feel ill - which would be likely to decrease eating.

While a whole host of peptides are thought to be involved in satiety, two have been found to play a role in hunger. Neuropeptide Y (NPY) and galanin both cause eating when injected into the paraventricular nucleus of the hypothalamus. NPY creates a hunger for carbohydrates and galanin for fats. Both decrease metabolism and increase fat production, suggesting they play a role in combating starvation. How does this work to regulate eating outside of a lab? Food deprivation results in an increase in NPY levels and eating decreases NPY levels. If NPY receptors in the hypothalamus are blocked, eating caused by NPY or deprivation is not seen.

What role do neurotransmitters play with respect to eating? It turns out that serotonin inhibits food intake, especially carbohydrate ingestion. Why is this so? One possibility is that serotonin inhibits NPY. There are numerous theories for how serotonin produces this effect on food intake. To make this situation more murky, there is counterintuitive findings that many SSRI, antidepressants that increase serotonin function also increase hunger and subsequent weight gain.

Ghrelin Effects on Hunger and More

Much of the research and findings regarding the role of the chemical ghrelin has focused on its ability to stimulate hunger. In fact, it is a significant signal for hunger that is based on both digestive properties in the gut and the preparation for incoming food.

Colldén, Tschöp, & Müller (2017) conducted a comprehensive review of the role of the chemical ghrelin on eating and a variety of other effects. As they point out, ghrelin is unique in terms of gut hormones in that it is the only one which can directly stimulate eating behavior and weight gain by acting on CNS mechanisms. They also describe a variety of additional effects that ghrelin is capable of influencing, some related to hunger and satiety and others not. Among these are ghrelin's ability to affect "enhanced gastric acid secretion and gastric motility, taste sensation, stress and anxiety, the sleep/wake cycle, glucose metabolism, and brown fat thermogenesis."

Colldén et al. (2017) go on to point out that, "Due to these and numerous other beneficial effects on systems metabolism... the endogenous ghrelin system is widely considered a promising approach to treat a variety of metabolic complications, most prominently ... pathological underweight associated with anorexia nervosa or cancer cachexia.”

From Set-Point to Settling Point

If you accept that a set-point theory does not explain our day-to-day eating behavior, what about the notion of a set-point as an explanation for why we can't seem to lose those last 5 pounds? We certainly tend to maintain a relatively constant body weight - why is that? And should we listen to our bodies? Should you eat whenever your body tells you to?

While these observations may suggest that we ultimately seek to defend a particular level of body fat, another notion is that we maintain a weight at which all the factors that influence body weight reach an equilibrium - a so-called "settling point".

Determining What to Eat

Let's look more closely at what determines the specifics of eating behavior. What we find is that, despite the findings with non-human subjects, human eating behavior has little to do with energy stores. What we do see is natural preferences for food that would facilitate survival in times of energy need - what types of food taste good? Sweet and fatty foods are energy dense and our cravings for them make sense from an evolutionary perspective - there was a time when we had to literally work for our food (hunting and gathering) as opposed to opening the refrigerator or placing an order for delivery. At the same time, bitter and sour tastes are typically associated with toxins. So, we have species-typical taste preferences and aversions (dislikes).

In addition to our inherited preferences, we also have those that are learned. We learn to eat what those around us eat - that which is familiar to us is going to be more appealing. Even if you like to try new things, I'm sure that there are limits to what you will eat.

How does an animal in the wild know what to eat in order to get the nutrients it needs? Researchers have looked at what happens when a diet lacks a nutrient and found that animals will respond - they will seek out variety when not getting all the needed nutrients and develop aversions to (dislike of) foods lacking in some nutrient. Most nutrients can't be tasted - especially with our diet today. But we do see cravings and desires at certain times - perhaps because those foods meet a need. Perhaps pickles have some benefit during pregnancy. And maybe ice cream fills a need created by a broken heart. Theoretically, we should have some ability to select the right foods, as we see in animals. But perhaps the learned elements of our eating (eating at meal times, clean your plate) have disrupted the body's ability to direct our eating choices. Further complicating ensuring we consume a balanced diet are personal decisions to restrict the types of foods eaten.Detecting Satiety

What determines how much we eat? How do we get satiety, what makes us feel "full"? Food in the body can induce satiety, but so can simply causing the stomach to distend - as was initially demonstrated in the early 1900's by researchers who observed the impact of inflating and deflating a swallowed ballon on hunger pangs (Cannon and Washburn, 1912). The fact is that the size of the stomach impacts how much one eats. Satiety created by food ingestion does seem to be dependent on nutritive density - to some degree food ingestion will be altered when the caloric content is changed. If you increase or decrease the calories per unit volume of food, animals will adjust their diet accordingly. Yet other studies have demonstrated with the use of sham feeding (where an animal feeds, but the food is ultimately not digested or absorbed) that the changes in food ingestion are not merely due to changes in the immediate caloric impact of the food.

We all know that we do respond to how food tastes - and we get tired of eating even those things that we do like - as studies of sensory-specific satiety have demonstrated. Rats (and humans) will eat more when presented with a varied diet of tasty food - a cafeteria diet. Here you see the incentive value of food overriding the normal mechanisms that control food intake.

Physiological Mechanisms of Hunger and Eating

There are a number of physiological mechanisms that serve as the basis for hunger. When our stomachs are empty, they contract. Typically, a person then experiences hunger pangs. Chemical messages travel to the brain, and serve as a signal to initiate feeding behaviour. When our blood glucose levels drop, the pancreas and liver generate a number of chemical signals that induce hunger (Konturek et al., 2003; Novin, Robinson, Culbreth, & Tordoff, 1985) and thus initiate feeding behaviour.

For most people, once they have eaten, they feel satiation, or fullness and satisfaction, and their eating behavior stops. Like the initiation of eating, satiation is also regulated by several physiological mechanisms. As blood glucose levels increase, the pancreas and liver send signals to shut off hunger and eating (Drazen & Woods, 2003; Druce, Small, & Bloom, 2004; Greary, 1990). The food’s passage through the gastrointestinal tract also provides important satiety signals to the brain (Woods, 2004), and fat cells release leptin, a satiety hormone.

Controlling the size of the stomach or the fullness of it can be used to help regulate eating. Bariatric surgery involves modifying the digestive system to achieve weight-loss. Approaches to such surgeries are varied, but decreasing the amount of food the stomach can hold is one such approach. Although recognized as an effective long-term approach for many, surgery may not be an option for many with a need for weight loss. Today, intragastric balloons are an alternative to surgical interventions.

The various hunger and satiety signals that are involved in the regulation of eating are integrated in the brain. Research suggests that several areas of the hypothalamus and hindbrain are especially important sites where this integration occurs (Ahima & Antwi, 2008; Woods & D’Alessio, 2008). Ultimately, activity in the brain determines whether or not we engage in feeding behavior.

The Role of the Hypothalamus

The hypothalamus plays a very important role in eating behavior. It is responsible for synthesizing and secreting various hormones. The lateral hypothalamus (LH) is concerned largely with hunger and, in fact, lesions (i.e., damage) of the LH can eliminate the desire for eating entirely - to the point that animals starve themselves to death unless kept alive by force feeding (Anand & Brobeck, 1951). Additionally, artificially stimulating the LH, using electrical currents, can generate eating behavior if food is available (Andersson, 1951).

Activation of the LH can not only increase the desirability of food but can also reduce the desirability of nonfood-related items. For example, Brendl, Markman, and Messner (2003) found that participants who were given a handful of popcorn to trigger hunger not only had higher ratings of food products, but also had lower ratings of nonfood products—compared with participants whose appetites were not similarly primed. That is, because eating had become more important, other non-food products lost some of their value.

While the feeling of hunger gets you to start eating, the feeling of satiation gets you to stop. Hunger and satiation are two distinct processes, controlled by different circuits in the brain and triggered by different cues. Distinct from the LH, which plays an important role in hunger, the ventromedial hypothalamus (VMH) plays an important role in satiety. Though lesions of the VMH can cause an animal to overeat to the point of obesity, the relationship between the LH and the VMH is quite complicated. Rats with VMH lesions can also be quite finicky about their food (Teitelbaum, 1955).

Is it that simple? Is the LH the key to hunger and the VMH the source of satiation (satiety)?

Evidence supporting the LH as a hunger center and the VMH as a satiety center:

• Lesioning (destroying) the lateral hypothalamus leads to anorexia (loss of appetite) and aphagia (absence of eating). At the same time, stimulating this region produces both eating and drinking. If you need a way to remember which is which - if you lesion the LH you get a lean hamster. If you lesion the VMH you get a very meaty hamster.
• Lesioning the ventromedial hypothalamus leads to hyperphagia (excessive eating) and weight gain. And stimulation of the VMH suppresses eating.

Evidence against the LH as a hunger center and the VMH as a satiety center:

• Lesions of the LH interfere with all motivated behaviors, not just feeding. In other words, perhaps the LH is a motivation center as opposed to a hunger center.
• Lesions of the VMH suppress the activity of sympathetic nervous system and increase the activity of the parasympathetic nervous system. In other words, the body is in rest and restore mode. Rats with VMH lesions become picky eaters, preferring carbohydrates. Due to the increased PNS activity, there is no fasting phase of metabolism; they are never living off of their reserves - rats continue to eat as they are not using their energy stores.

Other brain areas, besides the LH and VMH, also play important roles in eating behavior. The sensory cortices (visual, olfactory, and taste), for example, are important in identifying food items. These areas provide informational value, however, not hedonic evaluations. That is, these areas help tell an organism what is good or safe to eat, but they don’t provide the pleasure (or hedonic) sensations that actually eating the food produces. While many sensory functions are roughly stable across different psychological states, other functions, such as the detection of food-related stimuli, are enhanced when the organism is in a hungry drive state.

After identifying a food item, the brain also needs to determine its reward value, which affects the organism’s motivation to consume the food. The reward value ascribed to a particular item is, not surprisingly, sensitive to the level of hunger experienced by the organism. The hungrier you are, the greater the reward value of the food. Neurons in the areas where reward values are processed, such as the orbitofrontal cortex, fire more rapidly at the sight or taste of food when the organism is hungry relative to if it is satiated.

Summary

Eating behavior is complicated, controlled by two systems, one that controls hunger and one that signals satiety. In other words, we have a system that turns hunger on and another that determines that the need has been met. The lateral hypothalamus plays a role in hunger and the ventromedial hypothalamus appears to play a central role in satiation. Further complicating the control of hunger is the presence of two ways of signaling an energy need, a system that responds to the available levels of fuel and responding to short-term need and one that monitors energy stores. In the short-term, levels of available glucose are monitored, while stored fats are the focus for the long-term system.

References

Cannon, W. B., & Washburn, A. L. (1912). An Explanation of Hunger. American Journal of Physiology-Legacy Content, 29(5), 441–454. https://doi.org/10.1152/ajplegacy.1912.29.5.441

Crossan K, Sheer AJ. Intragastric Balloon. [Updated 2022 Feb 3]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/N...?log$=activity

Gale, S. M., Castracane, V. D., & Mantzoros, C. S. (2004). Energy homeostasis, obesity and eating disorders: Recent advances in endocrinology. The Journal of Nutrition, 134(2), 295. http://dx.doi.org/10.14341/2071-8713-5181

Hall, K. D., Heymsfield, S. B., Kemnitz, J. W., Klein, S., Schoeller, D. A., & Speakman, J. R. (2012). Energy balance and its components: implications for body weight regulation. The American journal of clinical nutrition, 95(4), 989–994. https://doi.org/10.3945/ajcn.112.036350

Speakman, J. R., Levitsky, D. ., Allison, D.B., Bray MS, de Castro JM, Clegg DJ, Clapham JC, Dulloo AG, Gruer L, Haw S, Hebebrand J, Hetherington MM, Higgs S, Jebb SA, Loos RJ, Luckman S, Luke A, Mohammed-Ali V, O'Rahilly S, Pereira M, Perusse L, Robinson TN, Rolls B, Symonds ME, Westerterp-Plantenga MS. Set points, settling points and some alternative models: theoretical options to understand how genes and environments combine to regulate body adiposity. Dis Model Mech. 2011 Nov;4(6):733-45. doi: 10.1242/dmm.008698. PMID: 22065844; PMCID: PMC3209643.

Attributions

"Overview", "Set-Point Theories", "Determining What to Eat", "Detecting Satiety", "Hunger, Satiety, and the Body", and "Summary" (2022) (CC BY).

"The Human Digestive System" and "Nutrition" adapted from Samantha Fowler, S., Roush, R. & Wise, J, (2013). 16.2 Digestive System - Concepts of Biology. OpenStax. Retrieved April 24, 2022, from https://openstax.org/books/concepts-biology/pages/16-2-digestive-system (CC BY)

"Physiological Mechanisms of Hunger and Eating" adapted from Hunger and Eating by Edited by Leanne Stevens (CC BY-NC-SA, except where otherwise noted).

"The Role of the Hypothalamus" adapted from Bhatia, S. & Loewenstein, G. (2022). Drive states. In R. Biswas-Diener & E. Diener (Eds), Noba textbook series: Psychology. Champaign, IL: DEF publishers. Retrieved from http://noba.to/pjwkbt5h (CC BY-NC-SA)

"Ghrelin Effects on Hunger and More": Excerpt from Colldén, G., Tschöp, M., & Müller, T. (2017). Therapeutic Potential of Targeting the Ghrelin Pathway. International Journal of Molecular Sciences, 18(4), 798. MDPI AG. Retrieved from http://dx.doi.org/10.3390/ijms18040798, (CC BY).